A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Aflibercept in Patients With Metastatic Colorectal Cancer Who Have Failed First-Line Therapy
Overview
- Phase
- Phase 2
- Intervention
- aflibercept + FOLFIRI
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- CR-CSSS Champlain-Charles-Le Moyne
- Enrollment
- 14
- Locations
- 4
- Primary Endpoint
- A biomarker (in blood or tissue) that may be predictive of level of response to aflibercept
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a Phase II multi-center exploratory study to identify biomarkers predictive of clinical response to aflibercept in patients with metastatic colorectal cancer who have failed first-line therapy, consisting of an oxaliplatin-containing regimen in combination with bevacizumab. Patients will consent to a needle core biopsy of a liver metastatic lesion prior to starting treatment and blood samples will be collected from study patients during treatment.
An exploratory pharmacoeconomic analysis will be performed to evaluate productivity loss, quality of life and resource utilization while on treatment with aflibercept.
Detailed Description
This is a Phase II multi-center exploratory study to identify biomarkers predictive of clinical response to aflibercept in patients with metastatic colorectal cancer who have failed first-line therapy, consisting of an oxaliplatin-containing regimen in combination with bevacizumab. Patients will consent to a needle core biopsy of a liver metastatic lesion prior to starting treatment. This study will be open primarily at sites conducting the Q-CROC-01 study (NCT00984048), in which colorectal cancer patients receiving standard first-line treatment undergo a biopsy of a liver metastatic lesion before treatment and at resistance. The post-first-line treatment biopsy will be used as the pre-treatment biopsy for this trial. For patients not participating in the Q-CROC-01 study, patients will be required to undergo a liver needle core biopsy of a metastatic lesion before study treatment. Biopsies and blood samples will be collected from all study patients. An exploratory pharmacoeconomic analysis will be performed to evaluate productivity loss, quality of life and resource utilization while on treatment with aflibercept. A total of 52 patients will be enrolled, primarily at centers participating in the Q-CROC-01 study. The trial will close enrolment when 42 evaluable pre-treatment tumor biopsy samples have been obtained. Accrual of the total patient population is estimated to take 24-36 months with the estimated start date being February 2014.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically proven adenocarcinoma of the colon or rectum, with at least one liver metastasis site available for biopsy.
- •Patients must have received only one prior chemotherapeutic regimen for metastatic disease. This prior chemotherapy must be an oxaliplatin containing regimen (in combination with bevacizumab). Patients who did not receive bevacizumab in their first-line treatment regimen may also be considered.
- •Metastatic disease that is not amenable to potentially curative treatment.
- •Measurable metastatic disease and evaluable disease.
- •Normal coagulation profile (PT, PTT, INR).
- •Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
- •Age ≥ 18 years.
Exclusion Criteria
- •More than 1 prior chemotherapy regimen for metastatic colorectal cancer. Previous adjuvant FOLFOX based chemotherapy is allowed.
- •Relapse from adjuvant treatment within 6 month of completion of adjuvant chemotherapy.
- •Less than 42 days elapsed from prior major surgery to the time of registration.
- •Inadequate or unusable tissue as the only tissue available for biopsy.
- •Any of the following within 3 months of registration: Grade 3-4 gastrointestinal bleeding/hemorrhage, diverticulitis, pulmonary embolism, inflammatory or infections bowel disease, treatment resistant peptic ulcer disease, colitis, erosive esophagitis or gastritis, uncontrolled thromboembolic event.
- •Prior intolerance to bevacizumab due to toxicity.
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency.
- •Gilbert's Syndrome.
- •Occurrence of deep vein thrombosis within 4 weeks, prior to registration.
- •Any of the following within 6 months prior to registration; myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack.
Arms & Interventions
aflibercept and FOLFIRI
aflibercept and FOLFIRI
Intervention: aflibercept + FOLFIRI
Outcomes
Primary Outcomes
A biomarker (in blood or tissue) that may be predictive of level of response to aflibercept
Time Frame: 3 years
A biopsy from a liver metastasis will be taken at baseline for discovery of biomarkers that correlate with response to aflibercept. Genomic material (DNA and RNA) will be isolated from all biopsies. Batched analysis will be performed at the end of the study with the evaluable samples for multiplex biomarker discovery. Patient's biomarker status at baseline will be correlated with treatment effect on PFS and response (including response rate and disease control rate) to explore which biological targets may be particularly important in defining the appropriate treatment population for aflibercept.
Secondary Outcomes
- Number of participants with adverse events(3 years)
- The quality of life impact of treating with FOLFIRI in combination with Aflibercept(From date of registration until progression of disease assessed up to 36 months)
- Response rate(3 years)
- Progression free survival (PFS)(Time from registration to progressive disease (up to 3 years))
- Disease control rate(3 years)