Adjuvant Aflibercept for Metastatic Colorectal Cancer (C261)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Brown University
Rhode Island Hospital
The Miriam Hospital
University of California, San Diego
Montefiore Medical Center
University of Florida
Information provided by (Responsible Party):
howard safran, Brown University Identifier:
First received: August 7, 2012
Last updated: February 2, 2015
Last verified: February 2015
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.

Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Aflibercept
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: BrUOG C261:Single Agent Adjuvant Aflibercept for Patients With Resected or Ablated Metastatic Colorectal Cancer: A Randomized Phase II Study

Resource links provided by NLM:

Further study details as provided by Brown University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Quality of life by EORTC Quality Of Life Questionnaire for patients on adjuvant aflibercept. [ Time Frame: Every 4 months for up to 2 years ] [ Designated as safety issue: No ]
  • Biomarkers in peripheral blood and fresh and archived tumor tissue following adjuvant aflibercept. [ Time Frame: Required prior to randomization (prior to day 1) ] [ Designated as safety issue: No ]

Estimated Enrollment: 69
Study Start Date: December 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aflibercept
Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years
Drug: Aflibercept
Aflibercept: 4mg/kg IV q2weeks until progression for a maximum of 2 years
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.

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01669720

Contact: Kayla Rosati, EdM 401-863-3000

United States, California
UCSD Recruiting
San Diego, California, United States, 92103
Contact: Kayla Rosati, EdM    401-863-3000   
Principal Investigator: Andrew Lowy, MD         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Kayla Rosati, EdM    401-863-3000   
Principal Investigator: Thom George, MD         
United States, New York
Montefiore Not yet recruiting
Bronx, New York, United States, 10467
Contact: kayla Rosati, EdM    401-863-3000   
Principal Investigator: Lakshmi Rajdev, MD         
United States, Rhode Island
Rhode Island Hospital (East Greenwich and Newport) Recruiting
Providence, Rhode Island, United States, 02903
Contact: Howard Safran, MD   
Principal Investigator: Howard Safran, MD         
The Miriam Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Howard Safran, MD   
Principal Investigator: Howard Safran, MD         
Sponsors and Collaborators
Brown University
Rhode Island Hospital
The Miriam Hospital
University of California, San Diego
Montefiore Medical Center
University of Florida
Principal Investigator: Howard Safran, MD Brown University Oncology Research Group
  More Information

No publications provided

Responsible Party: howard safran, Principal Investigator, Brown University Identifier: NCT01669720     History of Changes
Other Study ID Numbers: BrUOG C261
Study First Received: August 7, 2012
Last Updated: February 2, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Brown University:
Colorectal Cancer
Resected or Ablated Metastatic Colorectal Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site
Rectal Diseases processed this record on December 01, 2015