Adjuvant Aflibercept for Metastatic Colorectal Cancer

NCT ID: NCT01669720

Last Updated: 2020-02-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2016-01-31

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aflibercept

Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years

Group Type: EXPERIMENTAL

Aflibercept

Intervention Type: DRUG

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

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Aflibercept

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rhode Island Hospital

OTHER

Sponsor Role: collaborator

The Miriam Hospital

OTHER

Sponsor Role: collaborator

Lifespan

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: collaborator

Montefiore Medical Center

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

Brown University

OTHER

Sponsor Role: lead

Responsible Party

howard safran

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Howard Safran, MD

Role: PRINCIPAL_INVESTIGATOR

Brown University

Locations

Rhode Island Hospital (East Greenwich and Newport)

Providence, Rhode Island, United States

The Miriam Hospital

Providence, Rhode Island, United States

Countries

United States

Other Identifiers

BrUOG C261

Identifier Type: -

Identifier Source: org_study_id