Adjuvant Aflibercept for Metastatic Colorectal Cancer (C261)

• ClinicalTrials.gov Identifier: NCT01669720
• Recruitment Status: Terminated
• First Posted: August 21, 2012
• Results First Posted: March 10, 2016
• Last Update Posted: February 17, 2020
• Sponsor: Brown University
• Collaborators: Rhode Island Hospital; The Miriam Hospital; Lifespan; University of California, San Diego; Montefiore Medical Center; University of Florida; Sanofi
• Information provided by (Responsible Party): howard safran, Brown University

Tracking Information

• First Submitted Date: August 7, 2012
• First Posted Date: August 21, 2012
• Results First Submitted Date: January 8, 2016
• Results First Posted Date: March 10, 2016
• Last Update Posted Date: February 17, 2020
• Study Start Date: December 2012
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 11, 2016)

Number of Patients Who Progressed [ Time Frame: Every 3 months until disease progression (for up to 2 years). ]

Disease free survival in patients with advanced colorectal cancer who have undergone resection/ablation of all metastatic sites.

• Original Primary Outcome Measures (submitted: August 17, 2012): Disease free survival in patients with advanced colorectal cancer who have undergone resection/ablation of all metastatic sites. [ Time Frame: Every 3 months until disease progression with no estimated time period ]

Current Secondary Outcome Measures (submitted: May 23, 2018)

Number of Participants Who Experienced a Toxicity Profile of Adjuvant Ziv-aflibercept, up to 2-years of Duration, for Patients Who Previously Received Systemic Perioperative Therapy (Regimen) and Surgical Resection/Ablation. [ Time Frame: Throughout study treatment until 30 days post off study, approximately 2 years ]

Toxicity defined by CTCAE Version 4.0 toxicities

• Original Secondary Outcome Measures (submitted: August 17, 2012): Adverse events for patients receiving adjuvant aflibercept, up to 2-years of duration, for patients who previously received systemic chemotherapy and surgical resection/ablation. [ Time Frame: Every 2 weeks for up to 2 years ]
• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: August 17, 2012)

• Quality of life by EORTC Quality Of Life Questionnaire for patients on adjuvant aflibercept. [ Time Frame: Every 4 months for up to 2 years ]
• Biomarkers in peripheral blood and fresh and archived tumor tissue following adjuvant aflibercept. [ Time Frame: Required prior to randomization (prior to day 1) ]

Descriptive Information

• Brief Title: Adjuvant Aflibercept for Metastatic Colorectal Cancer
• Official Title: BrUOG C261:Single Agent Adjuvant Aflibercept for Patients With Resected or Ablated Metastatic Colorectal Cancer: A Randomized Phase II Study
• Brief Summary: The main purpose of this study is to evaluate if aflibercept can reduce the chance that metastatic (spread of) colorectal cancer can grow back after finishing standard treatment. The study will also look at the side effects of aflibercept and the effect on quality of life.

Detailed Description

There are over 1.2 million new cases of colorectal cancer and 600,000 deaths worldwide. The liver is the dominant site of metastases. Approximately 20-25% of patients with advanced colorectal cancer will be candidates for resection/ablation of all sites of metastatic disease.1 Unfortunately, despite resection/ablation of all metastatic sites only about 20% of these patients are ultimately cured.1 An effective adjuvant agent would prevent tumor recurrence.

Aflibercept and bevacizumab are effective when combined with FOLFIRI for metastatic colon cancer. Neither has been tested in a randomized study in the adjuvant setting for patients with resected metastatic disease. Since aflibercept more effectively inhibits all forms of VEGF including VEGF-A, VEGF-B and PIGF, in striking contrast to bevacizumab which inhibits only VEGF-A, aflibercept likely will be more effective than bevacizumab as a single agent in the adjuvant metastatic setting. Therefore, we propose a randomized study of adjuvant aflibercept for patients metastatic colorectal cancer who have received 10-12 cycles of perioperative FOLFOX and have had had a complete response to all sites of metastases after chemotherapy and local modalities such as surgical resection or ablation. SBRT may also be used to produce a complete response in a metastatic site not easily amenable to surgery or ablation. Only patients with very high risk of recurrence, defined as 3 or more metastatic sites, will be included in this study.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colorectal Cancer

Intervention

Drug: Aflibercept

Aflibercept: 4mg/kg IV q2weeks until progression for a maximum of 2 years

Study Arms

• Experimental: Aflibercept
  Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years
  Intervention: Drug: Aflibercept
• No Intervention: Observation
  Patients will be randomized 2:1 to receive Aflibercept. Patients who are randomized to observation will be followed per the study table, but will receive no intervention.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 11, 2015): 10
• Original Estimated Enrollment (submitted: August 17, 2012): 69
• Actual Study Completion Date: January 2016
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

3.1.1 First-line treatment of metastatic colorectal cancer with 3 or more metastases 3.1.2At least 10 cycles of combination therapy with an oxaliplatin or irinotecan based regimen per institutional preference (patients may receive 6 cycles, go to surgery, then complete 4 cycles, they may complete all 10 (or more) prior to surgery, or receive any combination as long as they receive at least 10 cycles. ) 3.1.3 Resection or ablation of all metastatic sites that have not achieved complete response with perioperative therapy (regimen). The sequencing of resection, ablation, and 10-12 cycles of combination therapy (regimen) with an oxaliplatin or irinotecan based regimen may be performed according to standard institutional procedure.

3.1.4 Patients achieving a complete response in a metastatic site by stereotactic body radiation are eligible if the site was not easily accessible by surgery or ablation and a complete response was achieved.

3.1.5 No severe, uncontrolled concurrent illness that would interfere with protocol therapy.

3.1.6 No known CNS disease 3.1.7 ECOG Performance Status 0-2 3.1.8 No chemotherapy or radiation therapy within last 3 weeks 3.1.9 For patients who had 3 months of perioperative therapy (regimen), then surgery, then 3 months of therapy (regimen), patients must be off therapy for no more than 8 weeks prior to randomization. For patients who had all their therapy and then surgery, they must be no more than 8 weeks from surgery prior to randomization.

3.1.10 No concurrent anticancer therapy. 3.1.11 Absolute neutrophil count ≥ 1,500/uL, Hgb > 9.0 g/dl, platelet ≥ 100,000/uL.

3.1.12 Total bilirubin ≤ 1.5x upper limit of normal (ULN) and AST or ALT ≤ 5x ULN; 3.1.13 Creatinine < 1.5 x ULN 3.1.14 Life expectancy of at least 12 weeks. 3.1.15 Age ≥ 18 years 3.1.16 Women of childbearing potential must have a negative pregnancy test. 3.1.17 Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.

3.1.18 Voluntary written informed consent.

Exclusion Criteria:

3.2.1 Residual metastatic disease after resection/ablation 3.2.2 Clinically significant cardiac disease (e.g., uncontrolled hypertension [blood pressure of >160/90 mmHg on medication], history of myocardial infarction within 6 months,), New York Heart Association (NYHA) Class II or greater congestive heart failure within 6 months, unstable arrhythmia. Patients with an atrial arrhythmia must have this condition well controlled on stable medication. Patients with current or recent (within 6 months) unstable angina are also not eligible. Documentation of cardiac medical history to be provided.

3.2.3 Significant bleeding diathesis or coagulopathy 3.2.4 History of cerebral aneurysms or cerebral arteriovenous malformations. 3.2.5 Patients with recent (within 12 months) arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), or clinically significant peripheral artery disease should also be excluded.

3.2.6 Patients with a history of a gastrointestinal fistula or perforation. 3.2.7 Women who are breast-feeding. 3.2.8 Patients who have undergone major surgery, chemotherapy, or radiotherapy within the last 3 weeks.

3.2.9 Patients on concurrent anticancer therapy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01669720
• Other Study ID Numbers: BrUOG C261
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: howard safran, Brown University
• Original Responsible Party: Same as current
• Current Study Sponsor: Brown University
• Original Study Sponsor: Same as current

Collaborators

• Rhode Island Hospital
• The Miriam Hospital
• Lifespan
• University of California, San Diego
• Montefiore Medical Center
• University of Florida
• Sanofi

Investigators

• Principal Investigator: Howard Safran, MD; Brown University

• PRS Account: Brown University
• Verification Date: February 2020