ACRIN Legacy Trials

The ACRIN legacy protocols and associated case report forms are available below as a reference and for data access requests for ancillary research projects. Researchers interested in accessing data from the ACRIN legacy trials should submit requests via the ECOG-ACRIN Data Access Committee. Please contact Patty Stebbins at for details regarding the ECOG-ACRIN Data Access Policy and application.

GI/GU Protocols

ACRIN Protocol 6659

MR Imaging and MR Spectroscopic Imaging of Prostate Cancer Prior to Radical Prostatectomy: A Prospective Multi-Institutional Clinicopathological Study

Principal Investigator: Jeffrey C. Weinreb, MD

Status: Results published

Main Objective: The primary aim of this protocol is to evaluate the accuracy of combined magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) performed at multiple institutions in the localization of prostate cancer and its incremental benefit on diagnostic accuracy when compared to MRI alone.

Participants: 134 persons with biopsy-proven adenocarcinoma of the prostate who are scheduled to undergo a radical prostatectomy at the participating institution.

Study Design Summary: Participants will undergo preoperative combined MRI/MRSI at one of seven institutions. Five independent readers will interpret all scans. Reference information will be derived from central pathological examination of surgical specimens. The primary endpoint is the evaluation of the presence of a tumor in a sextant of the prostate. The unit of analysis for the primary endpoint will be a single sextant.

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ACRIN Protocol 6664

The National CT Colonography Trial

Principal Investigator: C. Daniel Johnson, MD

Status: Results published

Main Objective: To clinically validate widespread use of computerized tomographic colongraphy (CTC) in a screening population for the detection of colorectal neoplasia.

Participants: Male and female outpatients, aged 50 years or older, scheduled for screening colonoscopy, who have not had a colonoscopy in the past five years.

Study Design Summary: The study addresses aspects of central importance to the clinical application of CTC in several interrelated but independent parts that will be conducted in parallel. In Part I, the clinical performance of the CTC examination will be prospectively compared in a blinded fashion to colonoscopy. In Part II, optimization of the CT technique will be performed in view of new
technological advances in CT technology. In Part III, lesion detection will be optimized by studying the morphologic features of critical lesion types and in the development of a database for computer-assisted diagnosis. In Part IV, patient preferences and cost-effectiveness implications of observed performance outcomes will be evaluated using a predictive model.

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ACRIN Protocol 6665/RTOG Protocol 0132

Phase II Trial of Neoadjuvant/Adjuvant STI-571 (Gleevec NSC 716051) for Primary and Recurrent Operable Malignant Gastrointestinal Stromal Tumors Expressing the KIT Receptor Tyrosine Kinase (CD117)

Principal Investigators: Burton Eisenberg, MD, RTOG Study Chair; Annick Van den Abbeele, MD, ACRIN Principal Investigator

Status: Results published

Main Objective: To provide a comprehensive evaluation of the effects of STI-571 on malignant GIST.

Participants: Individuals with a biopsy-proven diagnosis of potentially resectable primary or recurrent malignant gastrointestinal stromal tumor (GIST) or visceral or intraabdominal origin. There must be immunohistochemical documentation of KIT (CD117) expression in the tumor.

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ACRIN Protocol 6673

Multicenter Feasibility Study of Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma in Cirrhotic Patients

Principal Investigator: Gerald Dodd, III, MD

Status: Closed

Main Objective: To estimate the proportion of participants undergoing solitary or repetitive percutaneous radiofrequency ablation treatment sessions whose livers have no identifiable tumor by CT scan at 18 months following initiation of therapy.

Participants: Adult patients with cirrhosis and hepatocellular carcinoma in whom surgical resection is contraindicated will be potential candidates for this study. Eligible participants will have no previous or current treatment(s) for hepatocellular carcinoma by any method (no radiation therapy, chemotherapy, chemoembolization and cryoablation).

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ACRIN Protocol 6687

A Phase 2, Multicenter Evaluation of 18F-Fluoride PET as a Pharmacodynamic Biomarker for Dasatinib, a Src Kinase Inhibitor, in Men With Castration-Resistant Prostate Cancer and Bone Metastases (BMS #180-279)

Principal Investigator: Evan Y. Yu, MD

Status: Results published

Site Participation Note: This imaging protocol is a companion to the therapeutic protocol designed by Dr. Phillip G. Febbo of the University of California, San Francisco, entitled “Genomic Guided Therapy with Dasatinib or Nilutamide in Metastatic Castration-Resistant Prostate Cancer" and all sites must participate in both protocols.

Overview: The companion imaging trial allows eligible patients currently enrolled in Dr. Febbo’s therapeutic trial and receiving dasatinib to undergo 18F-fluoride PET imaging. Dr. Febbo’s therapeutic trial is supported through the Department of Defense (DoD) and Bristol-Meyers Squibb (BMS). The companion imaging protocol is funded by the National Cancer Institute and BMS.

Main Objective: The main objective of this trial is to determine whether changes in regional fluoride incorporation, measured by 18F-fluoride PET (SUV and Ki), will occur in both castration-resistant prostate cancer bone metastases and normal bone as a response to treatment with dasatinib.

Participants: Men with bone-metastatic castration-resistant prostate cancer (serum testosterone <50 ng/dL) who are participating in a separate therapeutic clinical trial (Febbo et al.) and receiving dasatinib as therapy are eligible for this companion 18F-fluoride PET imaging protocol. Participants from the Febbo trial receiving nilutamide only will not undergo 18F-fluoride PET imaging.

Study Design Summary: A total of 24 patients with castration-resistant prostate cancer bone metastases will be enrolled in this companion imaging biomarker study. It is anticipated that accrual will be completed in 1.5 years with a minimum of 16 patients enrolled in a year. A maximum of six DoD-affiliated institutions that are ACRIN-qualified for imaging will be participating in this trial.

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ACRIN Protocol 6690

A Prospective, Multicenter Comparison of Multiphase Contrast-Enhanced CT and Multiphase Contrast-Enhanced MRI for Diagnosis of Hepatocellular Carcinoma and Liver Transplant Allocation

Principal Investigator: Christoph Wald, MD, PhD

Status: Closed

Overview: ACRIN 6690 will examine the diagnostic accuracy of CT and MRI to detect hepatocellular carcinoma (HCC) in patients with chronic liver disease awaiting liver transplant. Imaging results will be compared with explant liver pathology analysis.

It is hypothesized that the combination of 1) state-of-the-art multiphase CT or MRI equipment, 2) contemporary multiphase contrast-enhanced imaging protocols, and 3) new diagnostic criteria will reduce false positive image diagnoses of liver cancer and ultimately lead to more informed treatment decisions and appropriate organ allocation and associated priority transplantation in the United States. This trial examines the new diagnostic criteria, a liver imaging policy draft, developed by the Organ Procurement and Transplantation Network (OPTN). Pre-qualification of CT and MRI scanners and images is required at sites wishing to participate. Participating sites will be transplant centers in the 11 OPTN transplant regions across the United States. Approximately 25 to 30 centers will participate.

Main Objectives: The main objective of the ACRIN 6690 trial is to compare the accuracy of radiologic staging of HCC by CT and MRI with the reference standard provided by explant pathology workup/staging of participants who undergo liver transplantation for treatment of HCC. Primary analysis will compare CT to MRI results at the lesion level using core laboratory interpretations of the imaging studies; secondary analysis will be performed at the patient level.

Participants: Patients diagnosed with HCC and listed or intended for listing for liver transplant surgery with priority MELD (Model for End-Stage Liver Disease) points based on the cancer diagnosis will participate. Patients may be waiting for a liver from a deceased donor to become available or be scheduled to undergo a living donor adult liver transplant. Patients will enroll in the trial after initial listing with HCC-exception points to the United Network for Organ Sharing (UNOS) waitlist or once site investigators confirm intent to list and complete the Declaration of Intent to List Source Document provided above. In the second scenario, no study-related imaging may be completed after baseline until UNOS waitlisting with priority MELD points is confirmed with ACRIN.

Study Design Summary: A total of 440 participants will be accrued to the ACRIN 6690 trial. A minimum of 200 of these participants are being asked to join the optional Eovist sub-trial, introduced with Amendment 2 to the trial protocol. All potential participants at sites conducting the EDRN Optional Ancillary Study of Multiplexed Biomarkers will be asked to consent to the blood draws associated with this sub-study.

For the main trial, each site will image (CT or MRI) a participant approximately every 90 days (or earlier) per the OPTN/UNOS HCC-exception point update requirements for their region. This imaging to evaluate disease is considered standard of care. This research trial requires that complementary imaging (CT or MRI, whichever imaging was not done as the standard of care) be completed at each 90-day interval. After baseline, this imaging needs to be completed within seven  days of the standard-of-care imaging that was done for that time interval. It is permissible to perform both imaging tests on the same day, the order of CT prior to MR is preferred. The goal is to have imaging with both modalities from within 90 days prior to transplantation available for comparison with explant pathology findings. Should a participant undergo local ablative therapy, CT and MRI should be completed no less than 28 days and no more than 60 days after each completed ablative therapy scheme.

The optional Eovist sub-trial adds a third imaging study to each time point. Details are provided beginning with Amendment 2.

The optional EDRN ancillary study for multiplexed biomarkers is introduced with Amendment 3 to the protocol and adds serial collection of blood for serum and plasma analysis at each of the imaging time points associated with the main study and at three months post-transplantation.

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Breast Protocols

ACRIN Protocol 6652

Digital Versus Film-Screen Mammography (DMIST)

Principal Investigator: Etta Pisano, MD

Status: Results published

Main Objective: To compare the diagnostic performance of digital mammography and screen-film mammography, as measured by the area under the ROC curve, sensitivity, specificity, and positive and negative predictive values in a prospectively enrolled screening cohort of asymptomatic women, across all digital mammography machine types.

Study Design Summary: All women will undergo both digital and screen-film mammography. Each examination will be interpreted independently and work-up will proceed based on the findings of either study. Truth regarding breast cancer status for all participants will be determined either through the results of breast biopsy, if that occurs, or as a result of one year of follow-up without clinical evidence of disease. An expert breast pathologist will reread all pathologic specimens.

Participants: Asymptomatic women presenting for screening mammography will be enrolled into this trial at 34 centers in the U.S. and Canada.

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ACRIN Protocol 6657/CALGB 150007

Contrast-Enhanced Breast MRI for Evaluation of Patients Undergoing Neoadjuvant Treatment for Locally Advanced Breast Cancer

Note: the ACRIN 6657 protocol amendment includes an extension to the original protocol to include additional aims as described below.

Principal Investigators: Nola M. Hylton, PhD, ACRIN Principal Investigator; Laura J. Esserman, MD, MBA, CALGB Study Chair

Status: Results published

Main Objective: Use MRI measurements of tumor response to uniquely identify two groups of participants who have statistically different three-year disease-free survival out of a group of participants with Stage III breast cancer who demonstrate a partial or minimal clinical response (as identified by physical examination) to neoadjuvant chemotherapy.

The objective of the ACRIN 6657 protocol extension is to investigate the usefulness of total choline concentration [tCho] measured by 1H MRS early in the course of treatment, for predicting pathologic response. Following completion of accrual to the original 6657 protocol, an additional group of patients meeting the same eligibility criteria as in the original protocol are being enrolled to the protocol extension. Three changes to the imaging protocol have been made: 1) addition of a single voxel 1H MRS acquisition and optional diffusion-weighted MRI acquisition to the MRI exam, 2) reduction of the number of (6657 study-related) imaging exams from four to three during the course of treatment, and 3) change of the timing of the post-first-cycle MRI/MRS exam.

Participants: Participants enrolled in the CALGB/Intergroup trial 49808 or participants receiving neoadjuvant chemotherapy consisting of an anthracyclin based regimen only or followed by a taxane and enrolled in CALGB Correlative Science trial 150007.

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ACRIN Protocol 6666

Screening Breast Ultrasound in High-Risk Women

Principal Investigator: Wendie Berg, MD, PhD

Status: Results published

Main Objective: To provide guidance to patients and practitioners on the role, if any, of screening breast ultrasound and the associated risk of an unnecessary biopsy.

Design Summary: We propose a multicenter trial of screening whole breast ultrasound using standardized technique and interpretation criteria in women at high risk of breast cancer. Annual screening for three years will be performed independent of mammography. The number of cancers seen on the initial screen as well as each of two subsequent screens will be assessed.

Additional Funding: Partial funding for this protocol is made available through a generous grant from the Avon Foundation.

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ACRIN Protocol 6667

MRI Evaluation of the Contralateral Breast in Women With a Recent Diagnosis of Breast Cancer

Principal Investigator: Constance Lehman, MD, PhD

Status: Results published

Main Objective: To determine the cancer yield of MRI in the contralateral breast of women with a recent breast cancer diagnosis and no known disease by mammography or clinical breast exam in the contralateral breast.

Participants: A total of 1,007 women with a recent history of breast cancer (negative or benign mammogram, and negative or benign clinical breast exam of the contralateral breast within 60 days prior to enrollment) will be enrolled into the trial at 22 centers in the U.S., Canada and Germany.

Study Design Summary: All women will undergo MR evaluation of the contralateral breast. Truth regarding breast cancer status will be determined through the results of a breast biopsy, if that occurs, or as a result of a 24-month follow-up without clinical evidence of disease.

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ACRIN Protocol 6688

Phase II Study of 3'-Deoxy-3'-18F Fluorothymidine (FLT) in Invasive Breast Cancer

VCU Principal Investigator: Paul R. Jolles, MD

ACRIN Principal Co-Investigators:
David Mankoff, MD, PhD, and Lale Kostakoglu, MD, MPH

Status: Results published

Main Objective: To evaluate the relationship between [18F]FLT uptake parameters and pathologic complete response to neoadjuvant therapy of the primary tumor in patients with locally advanced breast cancer.

Design Summary: Patients with locally advanced breast cancer who are candidates for primary systemic (neoadjuvant) therapy and for whom subsequent definitive surgery is planned (according to current clinical guidelines) may be eligible for this trial. Participants will be required to have three two-day imaging sessions using FLT and FDG-PET/CT to evaluate therapy response (baseline, mid-treatment, and just prior to surgical resection of residual tumor).

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ACRIN Protocol 6691

Monitoring and Predicting Breast Cancer Neoadjuvant Chemotherapy Response Using Diffuse Optical Spectroscopic Imaging (DOSI)

Principal Investigator: Bruce J. Tromberg, PhD

Status: Results published

Main Objective: DOSI will be used to evaluate the patient’s response to chemotherapy. The primary aim of this clinical trial is to determine whether the baseline to mid-therapy changes in the DOSI measurement of the quantitative tumor tissue optical index (TOI) can predict final complete pathologic response in breast cancer patients undergoing pre-surgical neoadjuvant chemotherapy. The secondary aims investigate the correlation between additional DOSI quantitative measurements of tumor biochemical composition obtained at other timepoints, the full range of pathologic response (i.e., complete, partial and non-response) and any corresponding imaging measurements.

Participants: Women are eligible for this trial if they have been diagnosed with breast cancer by clinical breast examination, standard-of-care diagnostic imaging, or initial tissue biopsy (confirmed by local site pathologist), and are scheduled to receive neoadjuvant chemotherapy followed by surgery.

Limited Site Participation
This is a limited participation study. The study is a joint effort between ACRIN and the NCI Network for Translational Research of the Interdisciplinary (NTROI) Research Consortium. All sites will use
NTROI standardized DOSI specifications and procedures, standard-of-care and/or other MRI imaging, and standard-of-care histopathology to assess pathological response. A total of seven NTROI clinical sites with identical DOSI instruments and procedures will participate: University of California, Irvine; University of California, San Francisco; University of Pennsylvania; Dartmouth; Harvard/Massachusetts General Hospital; Boston University; and M. D. Anderson Cancer Center.

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ACRIN Protocol 6698

Diffusion Weighted MR Imaging Biomarkers for Assessment of Breast Cancer Response to Neoadjuvant Treatment: A sub-study of the I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis)

Participating Institutions: Only sites participating in the I-SPY 2 TRIAL consortium may participate in the ACRIN 6698 study.

Protocol Principal Investigators:
Nola Hylton, PhD
Savannah Partridge, PhD
Mark Rosen, MD, PhD
Thomas Chenevert, PhD

Status: Results published

Overview: The objective of ACRIN 6698 study is to determine if diffusion weighted magnetic resonance imaging (DW-MRI) is effective for measuring breast tumor response to neoadjuvant treatment and if response measured by DWI early in the course of taxane-based therapy is predictive of pathologic response. ACRIN 6698 will be performed as a sub-study to the ongoing I-SPY 2 breast cancer neoadjuvant treatment trial.

Main Objectives: This trial's primary aim is to determine if the change in tumor apparent diffusion coefficient (ADC) value measured from each treatment timepoint to baseline using diffusion-weighted MRI (DW-MRI) is predictive of pathologic complete response. Secondary aims include: Determining if the combined measurement of change in tumor ADC value, change in tumor volume and change in peak signal enhancement ratio (SER) is predictive of pathologic complete response (pCR); investigating the relative effectiveness of the individual measurements, change in tumor ADC value, change in tumor volume, and change in peak signal enhancement ratio (SER) for predicting pathologic complete response in experimental treatment arms; and assessing the test-retest reproducibility of ADC measurements by DW-MRI applied to breast tumors.

Participants: Women who are eligible to participate in the I-SPY 2 TRIAL may co-enroll in the ACRIN 6698 imaging study.

Study Design: I-SPY 2 protocol includes four DCE-MRI scans as a measurement method for tumor response. In the current I-SPY 2 TRIAL, change in tumor volume, measured at multiple time points during treatment, will be used to update the patient randomization schema as the trial progresses. ACRIN 6698 contains advanced DWI acquisition parameters which will be included as part of the I-SPY 2 MRI examinations. ACRIN 6698 protocol will address the question of DWI sensitivity to drug effects via alterations in tumor water mobility, and will directly compare DWI-MRI to dynamic contrast-enhanced MRI (DCE-MRI) measurements of tumor microvascular behavior. The ACRIN 6698 imaging protocol will include the necessary elements for a high quality, quantitative imaging study, including protocol specifications, monitoring and quality control, image processing and contextual data analysis.

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ACRIN Protocol 6702

A Multi-Center Study Evaluating the Utility of Diffusion Weighted Imaging for Detection and Diagnosis of Breast Cancer

Principal Investigator: Savannah Partridge, PhD

Status: Results published

Overview: Magnetic resonance imaging (MRI) has become an important tool for breast imaging. Conventional breast MRI is highly sensitive for detecting cancer, but can also result in many false positives. Diffusion weighted imaging (DWI) can provide complementary information for lesion characterization by measuring the mobility of water molecules in tissue allowing an indirect assessment of tissue microstructure. The ACRIN 6702 study will evaluate DWI scans performed in women with breast lesions identified by conventional breast MRI. The study will determine whether an apparent diffusion coefficient (ADC) threshold can be defined for distinguishing benign and malignant lesions on DWI, assess the difference in ADC cutoffs for mass and non-mass lesions, and investigate the potential improvement in accuracy using techniques such as nonzero minimum b-value (to remove perfusion effects in the ADC measures) and normalized ADC measures (to account for variations in water content and other factors).

Primary Objective: To determine whether the Apparent Diffusion Coefficient (ADC), when used systematically in conjunction with conventional Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI), can reduce the biopsy rate by at least 20% while maintaining sensitivity.

Participants: Eligible participants are women 18 years or older who undergo a clinical breast MRI examination (including both DCE and DWI scans) by which a previously undiagnosed breast parenchymal lesion (BI-RADS 3, 4, or 5) is identified. Women undergoing high-risk screening and local staging for a recently diagnosed breast cancer (in whom an additional lesion distinct from the known cancer is detected on MRI) may be the most common candidates, but others meeting the criteria will not be excluded. Participants receiving neoadjuvant chemotherapy within six months prior to MRI or between the MRI and determination of lesion outcome will be excluded.

Study Design: This single-arm multi-institution study will recruit 100 women with breast lesions (BI-RADS 3, 4, or 5) identified by conventional breast DCE-MRI requiring either biopsy, surgical excision or short-interval imaging follow-up. Outcomes (benign or malignant) will be determined for each study lesion by means of biopsy, surgical excision and/or follow-up assessments at 30 days, six months, and 12 months after the MRI. It is anticipated that accrual for the study will take 12 months, with approximately 10 participating ACRIN-approved sites that acquire DWI in their standard clinical MRI protocol.

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GYN Protocols

ACRIN Protocol 6651

Role of Radiology in the Pretreatment Evaluation of Invasive Cervical Cancer

Principal Investigator: Hedvig Hricak, MD, PhD

Status: Results published

Main Objective: To compare the diagnostic performance of computed tomography (CT) and magnetic resonance imaging (MRI) to each other and to clinical FIGO staging in the primary evaluation of invasive cancer of the cervix.

Participants: Women with biopsy-documented invasive cervical cancer who are planning to have surgery.

Study Design Summary: Participants will undergo both CT and MRI before surgery. The first imaging study will take place within 20 days of registration. Scheduled surgery will follow the first imaging study within six weeks. CT and MR images will be collected and reviewed for image quality. A reader study will assess variability across radiologists. Participant questionnaires will be administered one week after last imaging to assess quality of life. A health utilities will be administered at one and 12 months after surgery. Follow-up information will be collected on each participant for a two-year period.

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GOG 0233/ACRIN Protocol 6671

Utility of Preoperative FDG-PET/CT Prior to Primary Chemoradiation Therapyto Detect Retroperitoneal Lymph Node Metastasis in Patients With Locoregionally Advanced Carcinoma of the Cervix (IB2, IIA =4 CM, IIB-IVA) or Endometrium (Grade 3 Endometrioid Endometrial Carcinoma; Serous Papillary Carcinoma, Clear Cell Carcinoma, or Carcinosarcoma (Any Grade); and Grade 1 or 2 Endometrioid Endometrial Carcinoma With Cervical Stromal Involvement Overt in Clinical Examination or Confirmed by Endocervical Curettage)

Principal Investigators:
Mostafa Atri, MD, ACRIN Principal Investigator
Michael Gold, MD, GOG Study Chair

Status: Results published

Primary Objectives:

  • To evaluate the diagnostic sensitivity and specificity of preoperative FDG-PET/CT imaging in identifying metastases to abdominal (common iliac, para-aortic, and para-caval) lymph nodes in patients with locoregionally advanced cervical carcinoma.
  • To evaluate the diagnostic sensitivity and specificity of preoperative FDG-PET/CT imaging in identifying metastases to retroperitoneal abdominal lymph nodes in patients with high-risk endometrial carcinoma.

Participants: Participating women must have either: primary, previously untreated, histologically confirmed, locoregionally advanced (IB2, IIA ≥4cm, IIB-IVA) invasive carcinoma of the cervix (any cell type) AND must be appropriate surgical candidates to undergo extra-peritoneal or laparoscopic lymph node sampling OR histologically confirmed Grade 3 endometrioid or non-endometrioid endometrial carcinoma (clear cell or serous papillary) or carcinosarcoma as diagnosed from an endometrial biopsy or dilation and curettage or histologically confirmed Grade 1 or 2 endometrioid endometrial carcinoma with cervical stromal involvement overt on clinical examination or confirmed by endocervical curettage AND must be appropriate surgical candidates to undergo hysterectomy and lymph node sampling.

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ACRIN Protocol 6682

Phase II Trial of 64Cu-ATSM PET/CT in Cervical Cancer

Principal Investigator: Farrokh Dehdashti, MD

Status: Closed

Main Objective: The objective of this study is to determine whether 64CU-ATSM used with PET/CT can distinguish patients with poorer survival outcomes from those with better survival outcomes prior to initiation of therapy.

Participants: Women with stages IB2–IVA, histologically confirmed, invasive squamous cell cervical carcinoma, who are scheduled to undergo radiation therapy and concurrent cisplatin chemotherapy.

Study Design Summary: A total of 100 female participants will be enrolled into the study at a minimum of three institutions.

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ACRIN Protocol 6695

Prognostic Perfusion CT in Gynecological Cancer: A Randomized Phase III Trial of Every-3-Weeks Paclitaxel versus Dose Dense Weekly Paclitaxel in Combination with Carboplatin with or without Concurrent and Consolidation Bevacizumab in the Treatment of Primary Stage I, II, III, or IV Epithelial Ovarian, Peritoneal, or Fallopian Tube Cancer

ACRIN Principal Co-Investigators: Chaan Ng, MD; Ting Yim Lee, PhD; and Robert Coleman, MD

Status: Results published

Overview: By adding functional imaging to the master treatment study, there is a potential to identify the quantitative functional parameters of perfusion CT that may act as early predictors of patient response to therapy, progression-free survival, and overall survival in ovarian cancer. The data obtained from early imaging are important to the development of early quantitative markers of tumor response and patient outcome to chemotherapy. This proof-of-concept study will demonstrate that derived functional parameters from perfusion CT imaging may act as surrogate markers of ovarian cancer response to chemotherapy and as predictors of patient outcomes.

Main Objectives: The main objectives of the imaging study (ACRIN 6695) is to determine changes in tumor perfusion parameters as quantified by: vascularity or blood volume (BV); perfusion or
blood flow (BF); mean transit time (MTT); and microvascular permeability or permeability surface area product (PS), from baseline (T0) to at the end of cycle 1 chemotherapy (T1), T0 to after the
start of cycle 2 chemotherapy/anti-angiogenic therapy (T2), and T1 to T2.

Study Design Summary: In this extension to the master GOG-0262 treatment study, ACRIN will perform three perfusion CT imaging examinations to evaluate the patient's response to
chemotherapy and anti-angiogenic therapy. Perfusion CT imaging will be performed at baseline (T0) prior to chemotherapy, at the end of cycle 1 chemotherapy (T1), and after the start of cycle 2
chemotherapy/anti-angiogenic therapy (T2).

The GOG-0262/ACRIN 6695 study was amended to allow ACRIN to accrue additional patients and meet its accrual goals for its primary analyses for the advanced imaging aims. As GOG has
completed its accrual for their needs, additional changes have been incorporated into the protocol. The changes include:

  • Patient participation in the ACRIN 6695 portion of the study is now a mandatory component of GOG 0262. A combined Informed Consent will be used in this extension.
  • Patients are eligible for participation if they are: suboptimally debulked disease (≥ 1cm) or plan to receive neoadjuvant chemotherapy followed by cytoreductive surgery. Optimally debulked patients (< 1cm) will not be eligible for participation.
  • No randomization will occur between chemotherapy arms. Chemotherapy regimens will be assigned at the discretion of the treating institution.
  • No translational research or quality of life research will be performed in the extension.

Participants: ACRIN will accrue data from 78 eligible and evaluable participants.

In addition to meeting the criteria of GOG 0262 (planned neoadjuvant chemotherapy followed by cytoreductive surgery or sub-optimally debulked disease [FIGO Stages I, II, III or IV]), patients must
have at least one tumor/metastasis satisfying the following criteria:

  • Lesion size larger than 1 cm residual (“suboptimally debulked” disease) in both the short and long axes in the abdomen or the pelvis as determined by non-contrast enhanced CT at first
    radiographic imaging;
  • At least half of the lesion has an attenuation of a least 10 HU in the qualifying pre-contrast CT scan;
  • At least half of the lesion has a maximum enhancement of at least 5 HU in the first CT perfusion scan

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Head and Neck Protocols

RTOG 0625/ACRIN Protocol 6677

Staging With MR Perfusion Imaging and MR Spectroscopy. ACRIN 6677 is conducted in collaboration with RTOG 0625: A Randomized Trial of Bevacizumab With Temozlomide in Recurrent Glioblastoma

ACRIN Principal Investigator:
Jerrold Boxerman, MD, PhD
RTOG Study Chair: Mark Gilbert, MD

Status: Results published

Study Objectives:
For central review -- to assess the agreement between local interpretation and central interpretation of the standard MRI on the six-month progression-free survival and to estimate the accuracy of local interpretation on the six-month progression-free survival using central review as the reference standard.

Advanced Imaging Component Objectives -- to assess the potential role of perfusion MRI and MR spectroscopy imaging as an early indicator of response to the therapy after two weeks following initiation of treatment with bevacizum and to assess the potential role of perfusion MRI and MR spectroscopy imaging as a prognostic indicator based on images taken before treatment, two weeks following initiation of protocol treatment, and after every two cycles of treatment.

Participants: Persons 18 years and older with a histologically proven intracranial glioblastoma or gliosarcoma. There must be pathologic or imaging confirmation of tumor progression or regrowth.

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ACRIN Protocol 6684

Multicenter, Phase II Assessment of Tumor Hypoxia in Glioblastoma Using 18F-Fluoromisonidazole (FMISO) With PET and MRI

Principal Investigator: Elizabeth R. Gerstner, MD

Status: Results published

Main Objective: To determine the association of baseline FMISO PET uptake (tumor to blood ratio, hypoxic volume) and MRI parameters (Ktrans, CBV) with overall survival, time to disease progression, and six-month progression-free survival in participants with newly diagnosed glioblastoma (GBM).

Participants: A total of 50 participants will be enrolled. A subset of 15 participants will have test-retest FMISO PET scans at baseline performed between one and seven days apart (both scans completed prior to initiation of chemoradiation). Each institution will not enroll more than 15 participants to this trial.

Study Design Summary: In this study, 50 participants with residual GBM will undergo FMISO PET and MRI scans after surgery and prior to start of chemoradiation (baseline). The subset of 15 participants will have two FMISO PET scans within one to seven days of each other to test reproducibility of FMISO PET; this substudy will continue to accrue until 15 participants have completed the two test-retest FMISO PET scans. Participants will then resume standard of care imaging for GBM per treating physician discretion, which will be submitted to ACRIN. Participants will be followed to assess for disease progression and survivorship until the end of the study.

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ACRIN Protocol 6685

A Multicenter Trial of FDG-PET/CT Staging of Head and Neck Cancer and its Impact on the N0 Neck Surgical Treatment in Head and Neck Cancer Patients

Principal Investigators: Val J. Lowe, MD, and Brendan C. Stack, Jr., MD, FACS

Status: Results published

Main Objective: The objective of this study is to determine the negative predictive value of PET/CT for the N0 neck based upon pathologic sampling of the neck lymph nodes and to determine PET/CT’s potential to change treatment of the N0 neck.

Participants: People with newly diagnosed head and neck squamous cell carcinoma being considered for surgical resection, with at least one side of the neck planned for dissection clinically N0, and at risk for occult metastasis (when risk based on clinical data is felt to be greater than 30%).

Study Design Summary: A total of 292 participants will be enrolled from a minimum of 10 ACRIN-qualified institutions, enrolling for approximately 24 months.

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RTOG 0825 ACRIN Protocol 6686

Phase III Double-Blind Placebo-Controlled Trial of Conventional Concurrent Chemoradiation and Adjuvant Temozolomide Plus Bevacizumab Versus Conventional Concurrent Chemoradiation and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

RTOG Principal Investigator: Mark R. Gilbert, MD

ACRIN Principal Investigator: Jerrold Boxerman, MD, PhD

Status: Results published

Overview: ACRIN 6686 is the advanced-imaging component of the RTOG 0825 trial. Pre-qualification of imaging scanners and images is required at RTOG sites wishing to participate in the advanced-imaging component. All eligible potential participants recruited at advanced-imaging sites must be asked to consent to advanced imaging. The advanced-imaging component comprises four DSC-
and DCE-MRI scans at baseline (T0), Week 3 (T1), Week 3 1 Day (T2), and Week 10 (T3).

Main Objectives: The main objectives of the ACRIN 6686 trial are to assess the association between overall survival and Ktrans change from T1 to T2 and to assess the association between overall survival and spin echo CBV changes from T1 to T2.

Participants: People with newly diagnosed, histopathologically confirmed glioblastoma (WHO Grade IV) able to undergo MRI who are accrued to ACRIN-qualified, RTOG sites participating in the ACRIN 6686 advanced-imaging component.

Study Design Summary: A total of 264 participants from the 720 RTOG-study patients will be accrued to the ACRIN 6686 advanced-imaging component of the trial.

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Thoracic Protocols

ACRIN Protocol 6654

Contemporary Screening for the Detection of Lung Cancer

Principal Investigator: Denise Aberle, MD

Status: Results published

Main Objective: To determine whether lung cancer screening using low-dose helical CT reduces lung cancer-specific mortality relative to screening with chest radiographs in a high-risk cohort.

Participants: Current or former cigarette smokers between the ages of 55 and 74 years without a history of lung cancer.

Study Design Summary: Prior to randomization, standardized eligibility, health, sociodemographic and spirometry will be performed. Some participants will provide blood, sputum and urine samples for archive at study entry and at the time of the second incidence screen. Study participants will be randomized into an Experimental and a Control group. The Experimental group will undergo screening with low-dose helical CT. The Control group will undergo screening with chest radiographs. Both groups will be screened annually for at least two incidence screens. Both groups will be contacted at six-month intervals to document interval health status. This protocol is conducted in close coordination with the Lung Screening Study of NCI. The two studies comprise the National Lung Screening Trial (NLST).

ACRIN 6654 (NLST) Data Access Instructions

NLST Clinical Data: Access to comprehensive NLST datasets (excludes QOL data) is available through the Cancer Data Access System (CDAS).

NLST CT Image Data: Access to CT images from NLST screening exams is available through the Cancer Imaging Archive (TCIA) website. TCIA’s site includes a query tool that lets users dynamically identify subpopulations of interest and download the CT images and clinical data on those subpopulations. The clinical data on TCIA are equivalent to the data available through CDAS.

NLST Biospecimen Data: Serial collections of blood components (plasma and buffy coat), urine and sputum from a subset of participants at each of the three annual NLST screening exams are available for ancillary research projects that will validate biomarkers of early lung cancer that are proven to have potential in preliminary testing. Researchers also can request access to resected tissues from trial participants with lung cancer.

Researchers interested in obtaining ACRIN-NLST biospecimens should review the [Biorepository Specimen Inventory Tables ] and contact to request details and instructions on the access request process.

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RTOG Protocol 0234/ACRIN Protocol 6668

Positron Emission Tomography Pre- and Post-treatment Assessment for Locally Advanced Non-small Cell Lung Carcinoma

Principal Investigator: Mitchell Machtay, MD

Status: Results published

Main Objective: The primary purpose of this study is to determine if the SUV measurement from FDG-PET imaging shortly after treatment is a useful predictor of long-term clinical outcome (survival) after definitive chemoradiotherapy.

Participants: Eligible patients are those older than 18 years with AJCC clinical stage IIB/III non-small cell lung carcinoma who are being planned for definitive concurrent chemoradiotherapy (inoperable disease).

Study Design Summary: A total of 250 participants will be enrolled, including at least 75 with stage IIB/IIIA and at least 75 with stage IIIB disease. A baseline whole-body FDG-PET scan will be performed. Follow up after chemoradiotherapy will comprise restaging of the disease and a second whole-body FDG-PET scan 12 to 16 weeks after the completion of radiotherapy (at least four weeks after adjuvant chemotherapy).

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ACRIN Protocol 6678

FDG-PET/CT as a Predictive Marker of Tumor Response and Patient Outcome: Prospective Validation in Non-small Cell Lung Cancer

Principal Investigator: Wolfgang Weber, MD

Status: Closed

Main Objectives:

  • To test whether a metabolic response, defined as a ≥ 25% decrease in peak tumor SUV post-cycle 1 of chemotherapy, provides early prediction of treatment outcome (tumor response and patient survival).
  • To determine the test-retest reproducibility of quantitative assessment of tumor FDG uptake by SUVs.
  • To evaluate in an exploratory analysis the time course of treatment induced changes in tumor FDG uptake.
  • To evaluate in an exploratory analysis changes in tumor volume during chemotherapy by multislice CT.

Participants: Eligible participants for this trial are patients with advanced NSCLC (for Groups A and B: Stage IIIB with pleural effusion or Stage IV, who are scheduled to undergo palliative
chemotherapy; for Group C, Stages IIIA, IIIB, or IV, with unspecified therapy) who meet the eligibility criteria. Patients with previously treated NSCLC may participate so long as they meet the eligibility criteria.

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RTOG Protocol 1106/ACRIN Protocol 6697

Randomized Phase 2 Trial of Individualized Adaptive Radiotherapy Using During-treatment FDG-PET/CT and Modern Technology in Locally Advanced Non-small Cell Lung Cancer (NSCLC)

Protocol Principal Investigators:
Feng-Ming (Spring) Kong, MD, PhD, RTOG 1106 Principal Investigator
Daniel Pryma, MD, ACRIN 6697 Principal Investigator

Status: In follow-up

Overview: The RTOG 1106/ACRIN 6697 clinical trial is evaluating if during the course of radiotherapy (RT) treatment information gained from a FDG-PET/CT scan can facilitate individualized adaptive therapy in patients with inoperable stage-III non–small-cell lung cancer (NSCLC). Please Note: Participating sites must be RTOG member institutions and ACRIN qualified.

Main Objectives:
RTOG 1106:
To determine whether tumor dose can be escalated to improve the freedom from local-regional progression (LRPF) rate at two years when an individualized adaptive RT plan is applied by the use of a FDG-PET/CT scan acquired at 40-46 Gy initial dose of RT in patients with inoperable or unresectable stage III NSCLC
ACRIN 6697: To determine whether the relative change in SUV peak from the baseline to the during-treatment FDG-PET/CT, defined as (during-treatment SUVpeak – baseline SUVpeak)/baseline SUVpeak x 100%, can predict the LRPF with a two-year follow up.

Participants: Patients must be > 18 and have FDG-avid (maximum SUV ≥ 4.0) and histologically or cytologically proven non-small cell lung cancer.

Study Design: The primary objective of RTOG 1106/ACRIN 6697 is to determine whether tumor dose can be escalated to improve the "freedom from local-regional progression" rate after two years of treatment using FDG-PET/CT scans to individualize adaptive RT plans.

All participants will undergo a baseline FDG-PET/CT scan as part of their treatment planning.

Participants in both arms will receive RT once a day five days a week for six weeks. After four weeks of treatment, participants of both arms will undergo a second FDG-PET/CT scan. Participants in the experimental arm will have the RT planning modified to provide as high a dose as possible to the residual metabolically active tumor while keeping doses to normal lung tissue constant (mean lung dose of 20 Gy) and doses to other adjacent organs within safe limits whereas participants in the control arm will complete the initial treatment as planned.

In a subset of the study’s participants, 18F-fluoromisonidazole (FMISO)-PET/CT will be conducted at baseline to identify the presence of hypoxia, which inhibits the production of the oxygen-free radicals that cause radiation to damage DNA and to kill tumor cells. The trial will test the use of imaging to identify hypoxic areas and to target those areas with higher levels of radiation. The important question is whether areas of hypoxia identified at baseline will contain residual disease at mid-treatment stage since it’s the slowest to die off.

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