Clinical trial NCT01669720: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic
Colorectal
Colorectal Cancer
Resected or Ablated Metastatic Colorectal Cancer
Lead sponsor: Brown University
Sponsor class: OTHER
Collaborators: name: Rhode Island Hospital
name: The Miriam Hospital
name: Lifespan
name: University of California, San Diego
name: Montefiore Medical Center
name: University of Florida
name: Sanofi
First posted: 2012-08-21
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Patients Who Progressed
timeFrame: Every 3 months until disease progression (for up to 2 years).
Secondary outcomes:
measure: 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.
timeFrame: Throughout study treatment until 30 days post off study, approximately 2 years
Other outcomes:
Locations:
city: Providence
country: United States
facility: Rhode Island Hospital (East Greenwich and Newport)
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
Study officials:
affiliation: Brown University
name: Howard Safran, MD
role: PRINCIPAL_INVESTIGATOR
References: