Rechallenge of Cetuximab Combined With Irinotecan as Third-line Chemotherapy in Patients With Metastatic Colorectal Cancer - Phase II Study (REGAIN)

A Phase II Study of Cetuximab Rechallenge in Combination With Irinotecan in Advanced Metastatic Colorectal Cancer Without KRAS or NRAS or BRAF Mutation (All Wild Type) for Patients Pretreated With FOLFIRI and Cetuximab in First Line With Stopping Cetuximab for Progressive Disease After a Previous Response (Partial Response or Complete Response) and After Treatment With a Fluoropyrimidine, Oxaliplatin Plus Bevacizumab Regimen

The main objective of this study is to evaluate the objective response rate at two months (complete disappearance of the disease and partial disappearance of the disease) obtained after administration of combination therapy with cetuximab and irinotecan in the patients with metastatic colorectal cancer.

Secondaries objectives will be assessed progression-free survival, overall survival, toxicity, quality of life.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: cetuximab; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clichy, France
    • Hôpital Beaujon
  • Contamine sur Arve, France
    • Centre Hospitalier Alpes Leman
  • Dijon, France
    • Centre Georges Francois Leclerc
  • La Roche/ Yon, France
    • CHD Vendee
  • Lyon, France
    • Hopital Prive Jean Mermoz
  • Marseille, France
    • Institut Paoli-Calmettes
  • Marseille, France
    • Hôpital Européeen
  • Nîmes, France
    • CHU Caremeau
  • Paris, France
    • Hopital Pitie Salpetriere
  • Paris, France
    • Hôpital Saint Antoine
  • Paris, France
    • Hopital Saint Louis
  • Paris, France
    • Hopital Tenon
  • Paris, France
    • CHU Cochin
  • Saint Brieuc, France
    • Clinique Armoricaine de Radiologie
  • Senlis, France
    • Groupe hospitalier Public du Sud de l'Oise -site de Senlis
  • Strasbourg, France
    • Centre de Radiothérapie - Clinique Sainte Anne
  • Suresnes, France
    • Hôpital Foch
  • Thonon les Bains, France
    • Hôpitaux du Léman
  • Tours, France
    • CHU Tours - Hôpital TROUSSEAU
  • Valence, France
    • Clinique Générale

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed and dated informed consent
• Histologically confirmed metastatic adenocarcinoma of the colon or rectum
• All Wild Type KRAS (exon 2 [codons 12-13], exon 3 [codons - 61]; exon 4 [codon 146]), NRAS (exon 2 [ codons 12-13] and exon 3 [codon 61) and BRAF (V600E) tumor ( local assessment performed either on primary tumor or metastasis)
• First line chemotherapy regimen with a fluoropyrimidine and Irinotecan (FOLFIRI) + cetuximab with initial partial or complete response and progressive disease (PD) with PD ≤ 6 weeks after the last administration of cetuximab
• Other line(s) of therapy(ies) including the following drugs: second line oxaliplatin based chemotherapy with fluoropyrimidines (5FU or capecitabine) + bevacizumab and eventually regorafenib (possible but not mandatory) and progression or limiting toxicity to the last therapy with a minimum of 4 months between last injection of cetuximab and inclusion in this study
• At least one measurable lesion ≥ 10 mm as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1 (All sites must be evaluated ≤ 28 days prior to the enrolment)
• Age ≥18 years
• World Health Organization (WHO) Performance status (PS) 0-2
• The patient has adequate organ function, defined as :

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dL, and platelets ≥ 100 x 109/L.Total bilirubin ≤ 1.5 times upper limit of normal value (ULN), serum alkaline phosphatase level < 5 times ULN, Serum creatinine level <150μM/l

• For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug
• Men and women are required to use adequate birth control during the study (when applicable) and until 6 months after the end of study treatment
• Registration in a national health care system (CMU included)

Exclusion Criteria:

• Previous chemotherapy other than adjuvant therapy with different combinations than those scheduled in first and second line treatment
• Presence of any KRAS, BRAF or NRAS mutation by allelic discrimination on tumor DNA
• Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiation of study treatment or a history of ventricular arrhythmia (treated or not)
• History or evidence of central nervous system metastasis (systematic CT-scan or MRI not mandatory if no clinical symptoms)
• Known allergy or hypersensitivity to cetuximab
• Previous or concurrent malignancy except for basal or squamous cell skin cancer, in situ carcinoma of the cervix, low-risk prostate cancer according to d'Amico classification or other solid tumors treated curatively and without evidence of recurrence for at least 5 years prior to the study
• Active or uncontrolled clinically serious infection
• Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
• Other serious and uncontrolled non-malignant disease
• Pregnancy
• Breast feeding
• Treatment with any other investigational medicinal product within 28 days prior to study entry
• Known Gilbert's syndrome
• Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine
• Concomitant use with St John's Wort
• Chronic inflammatory bowel disease and/or Bowel obstruction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: open label , single arm; cetuximab - irinotecan until progression or unacceptable toxicity	Drug: cetuximab; cetuximab 500mg/m²/ IV infusion, (q2w); Drug: Irinotecan; Irinotecan 180mg/m², in 500ml NaCl 0.9% solution, 90 min IV infusion (q2w)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR)	At 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Best response observed during investigational treatment combination. From the start of treatment until treatment failure	up to 27 months
Disease control rate (DCR)	The proportion of patients with tumor response (Complete response or partial response) or tumor stabilization as best response during study treamtent	up to 27 months
Progression-free survival (PFS)	Time from the date of inclusion to the date of the first progressive disease (RECIST criteria) or death (any cause)	up to 27 months
Duration of response (DOR)	Only for patients with tumor response (complete reposne or partial response) , from first confirmed response to first observed progression (PD) or death due to PD during study treatment	up to 27 months
Time to response (TTR)	Time from the date of inclusion to the date of the first confirmed CR or PR during study treatment	up to 27 months
Time to progression (TTP)	Time from the date of inclusion to the date of the first obseved progression (PD), or death due to progression during the study treatment	up to 27 months
Time to treatment failure (TTF)	Time from the date of inclusion to the date the decision was made to end the study treatment for any reason	up to 27 months
Duration of stable disease (DoSD)	Only for patient with a stable disease (SD) as best response during the study treatment, from date of inclusion to the first observed progression (PD) or death due to progression	up to 27 months
Overall survival (OS)	From the date of inclusion to the date of patient death, due to any cause, or to the last date the patient was known to be alive	up to 27 months
Adverse Events (CTCAE v.4.03)		Up to 27 months
Quality of life	Using EORTC Quality of Life Questionnaire - C30 (QLQ-C30) and the Dermatology Life Quality Index (DLQI ) questionnaires	Up to 27 months
Respose rate	RAS and BRAF status in circulating tumoral DNA	up to 27 months
PFS	RAS and BRAF status in circulating tumoral DNA	up to 27 months

Collaborators and Investigators

• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Investigators: Principal Investigator: Jean Marc GORNET, MD, Hopital Saint Louis

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: December 8, 2014
• First Submitted That Met QC Criteria: December 10, 2014
• First Posted (Estimate): December 15, 2014

Study Record Updates

• Last Update Posted (Actual): August 1, 2017
• Last Update Submitted That Met QC Criteria: July 29, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Cancer; Metastatic; Cetuximab; Irinotecan; Colorectal; Thrid-line
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Cetuximab
• Other Study ID Numbers: REGAIN C13-2