Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Aflibercept

Endothelial Growth Factors

Mitogens

Angiogenesis Inhibitors

Growth Inhibitors

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.

aflibercept + FOLFIRI

Benoit Samson, MD

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.

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.

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

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

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.

The time from the date of registration until the date of radiological disease progression assessed by RECIST 1.1 or until death due to any cause, even in the absence of radiological progression.

Defined as complete response (CR) and partial response (PR)

Defined as complete response (CR) + partial response (PR) + stable disease (SD).

Assessment of safety profile of aflibercept in combination with FOLFIRI: report of Adverse Events according to the NCI's Common Toxicity Criteria version 4.0

Quality of life will be evaluated by questionnaires completed by the patient.

Sanofi

Regeneron Pharmaceuticals

Quebec Clinical Research Organization in Cancer

CR-CSSS Champlain-Charles-Le Moyne

Symptoms and General Pathology

Recurrence

Micronutrients

Hematinics

Vitamins

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Folic Acid

Folinic Acid

Folate

Vitamin B9

Day 1. Aflibercept + FOLFIRI

* aflibercept(Zaltrap): 4 mg/kg IV infusion for over 1hr (Do not administer as an IV push or bolus)
* Folinic acid: 400 mg/m2 IV infusion for over 2 hours
* Irinotecan: 150 mg/m2 IV infusion for over 1 hours
* 5-FU: 400 mg/m2 IV bolus injection for over 5 minute
* 5-FU: 2400 mg/m2 IV continuous infusion for 46 hours every 2 weeks until progression disease or death or unacceptable toxicity

Aflibercept + FOLFIRI

Joong Bae Ahn, MD, PhD

Based on the pervious data, aflibercept in combination with FOLFIRI is one of the effective 2nd line treatment option in advanced colorectal cancer. In this study, we prospectively assess the efficacy of 2nd line aflibercept in combination with FOLFIRI in advanced colorectal cancer in terms of progression-free survival. We further assess the efficacy according to the type of 1st line treatment. plasma biomarker study (HGF, VEGF-A, VEGF-D, IFN-γ, Angiopoietin-2, sICAM-1, sVCAM-1, TIMP-1, PIGF (HS), IL-6 (HS), IL-8 (HS), sNeuropilin-1, Thrombospondin-2 , Osteopontin , sVEGFR1, sVEGFR2, sVEGFR3) , overall survival (OS)OS, objective response rate (ORR), and safety are also assessed as the 2ndary objectives.

This is a prospective, multicenter, open-label, single arm study. Patients will be considered "on study" upon signing the written informed consent form (ICF). The study consists of a baseline period, followed by a treatment period, consisting of 14-day treatment cycles, which will end by a 30-day Follow-up visit, which in turn, will be followed by a post-treatment follow-up period.

Patients will be evaluated for PFS then be followed on study until death or until cut-off date for final analysis of OS has been reached, whichever comes first.

During the 21-day baseline period, all baseline procedures will have to be performed within defined timelines, including review of eligibility criteria During the treatment period, the study treatment, aflibercept combined with FOLFIRI will be administered every 2 weeks unless a definitive treatment discontinuation criterion is met. Cycle lengths may be extended in case of unresolved toxicity.

Imaging to document tumor response and progressive disease will take place every 6 weeks and will continue to be done during the follow-up period in case of early study treatment discontinuation (i.e. prior to documented progression). Once disease progression is documented, patients will be followed every 2 months for survival status and collection of data regarding further anticancer therapy, until death or until the study cutoff date, whichever comes first.

The patients will be followed for safety for a minimum of 30 days following the last administration of the study treatment (30-day Follow-up visit). Beyond this date, all study drug related AEs and all SAEs should be followed until resolution/stabilization. Study drug-related AEs brought to the attention of the investigator at any time after the 30-day Follow-up visit should be recorded in the case report form (CRF).

Plasma Biomarker for Aflibercept in Advanced Colorectal Cancer

Efficacy and Biomarker Exploration of 2nd Line Aflibercept in Combination With FOLFIRI in Advanced Colorectal Cancer

progressive disease (PD) or death, whichever occurs first. Results will be summarized by arm

* Kaplan-Meier method for survival function estimate
* Stratified Cox proportional hazard regression for hazard ratio (HR) estimate

Yonsei University

Colonic Neoplasms

Herbal and Botanical

Oxaliplatin

Cola

RANIA BOUSTANY, Dr

CELESTE DAVID

Laurent Mineur, Doctor

RANIA BOUSTANY

Primary objective

- Evaluate the efficacy in terms of progression-free survival (PFS) of aflibercept in combination with FOLFIRI in patients treated routinely for metastatic colorectal cancer (mCRC) after failure of treatment with oxaliplatin + EGFR.

Secondary objective

* Evaluate the efficacy of aflibercept in combination with FOLFIRI on the 2-year overall survival rate and the objective response rate.
* Evaluate the tolerance profile of aflibercept in combination with FOLFIRI.

  * Observational study, national, multicenter, cohort, prospective without intervention on the therapeutic strategy.•

Inclusion criteria

* All patients expected to be treated with aflibercept in combination with FOLFIRI for a mCRC, after failure of treatment with oxaliplatin + anti-EGFR on the decision of the doctor (situation included in the framework of the MA of aflibercept) .
* Age ≥18 years
* Signature of the agreement for the collection of medical and personal data. (Patients who have received FOLFIRINOX in the first line metastatic are allowed) Note: Failure is defined as progression during or within 6 months after discontinuation of oxaliplatin

Exclusion criteria :

* Concurrent participation in a clinical trial
* Patients who have previously received anti-VEGF agents and / or aflibercept in one trial.
* Patients who received FOLFIRI in the first metastatic line.

ZETA : Prospective Observational Study

Non-comparative Prospective Observational Cohort Study Describing the Safety and Efficacy of Aflibercept Administered in Combination With FOLFIRI After Failure Under Oxaliplatin + Anti-EGFR Therapy in the Treatment of Patients With Metastatic Colorectal Cancer in Practice Common

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Identify Biomarkers of Clinical Response to Aflibercept in Patients With Metastatic Colorectal Cancer	NCT02045030	Metastatic Colo...	aflibercept + F...	18 Years -	CR-CSSS Champlain-Charles-Le Moyne
Plasma Biomarker for Aflibercept in Advanced Colorectal Cancer	NCT04810585	Recurrent or Me...	Aflibercept + F...	19 Years -	Yonsei University
ZETA : Prospective Observational Study	NCT03730558	Metastatic Colo...	aflibercept + F...	18 Years -	Institut Sainte Catherine
Study to Identify Biomarkers of Clinical Response to Aflibercept in Patients With Metastatic Colorectal Cancer	NCT02045030	Metastatic Colo...	aflibercept + F...	18 Years -	CR-CSSS Champlain-Charles-Le Moyne
ZETA : Prospective Observational Study	NCT03730558	Metastatic Colo...	aflibercept + F...	18 Years -	Institut Sainte Catherine

Spots Global Cancer Trial Database for aflibercept + folfiri