Study to Identify Biomarkers of Clinical Response to Aflibercept in Patients With Metastatic Colorectal Cancer

NCT02045030 | Terminated Phase 2

• 1 other identifier: Q-CROC-04
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

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.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic; colorectal; cancer; aflibercept; FOLFIRI

Outcome Measures

Primary Outcomes (1)

• A biomarker (in blood or tissue) that may be predictive of level of response to aflibercept

  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.

  3 years

Secondary Outcomes (5)

• Progression free survival (PFS)

  Time from registration to progressive disease (up to 3 years)

• Response rate

  3 years

• Disease control rate

  3 years

• 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

Study Arms (1)

aflibercept and FOLFIRI

EXPERIMENTAL

aflibercept and FOLFIRI

Drug: aflibercept + FOLFIRI

Interventions

aflibercept + FOLFIRI DRUG

Aflibercept (Sanofi and Regeneron) targets the Vascular endothelial growth factor (VEGF) pathway that is a composite decoy receptor based on VEGFR-1 and VEGFR-2 fused to an Fc segment of IgG1. In pre-clinical assessments, aflibercept results in stronger angiogenesis inhibition than bevacizumab, exhibiting at least 100-1000 times higher affinity to the circulating VEGFs. It is postulated that in vivo, the binding of these ligands to aflibercept results in the blockade of tumor angiogenesis along with pruning of existing tumor vascular elements and reduction of VEGF-driven vascular permeability. The expected outcome is reduced growth of primary and metastatic tumors by impeding the density of tumor vasculature and diminishing the abnormal leakiness of tumor vessels that supply matrix components to the cancer.

Also known as: aflibercept, FOLFIRI

aflibercept and FOLFIRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ECOG 0 or 1.
• 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.

You may not qualify if:

• 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.
• Contraindication to any of the components of the FOLFIRI chemotherapy regimen, as per investigators' judgement.
• Inadequate bone marrow function as follows:
• Absolute neutrophil count (ANC) \< 1.5x 109/L
• Platelet count \< 100 x 109/L
• Hemoglobin \< 90 g/L

Sponsors & Collaborators

• CR-CSSS Champlain-Charles-Le Moyne: lead
• Sanofi: collaborator
• Regeneron Pharmaceuticals: collaborator
• Quebec Clinical Research Organization in Cancer: collaborator

Study Sites (4)

CSSS Champlain-Charles-Le Moyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, H4J 1C5, Canada

Location

Related Publications (3)

• Wang TF, Lockhart AC. Aflibercept in the treatment of metastatic colorectal cancer. Clin Med Insights Oncol. 2012;6:19-30. doi: 10.4137/CMO.S7432. Epub 2012 Jan 4.

  PMID: 22253552 BACKGROUND

• Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42. doi: 10.1056/NEJMoa032691.

  PMID: 15175435 BACKGROUND

• Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausova J, Macarulla T, Ruff P, van Hazel GA, Moiseyenko V, Ferry D, McKendrick J, Polikoff J, Tellier A, Castan R, Allegra C. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012 Oct 1;30(28):3499-506. doi: 10.1200/JCO.2012.42.8201. Epub 2012 Sep 4.

  PMID: 22949147 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

aflibercept; IFL protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Benoit Samson, MD

  CSSS Champlain-Charles-Le Moyne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2014
• First Posted: January 24, 2014
• Study Start: January 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: November 16, 2016

Record last verified: 2016-08

Locations

CA (4)