Clinical trial NCT02316496: Rechallenge of Cetuximab Combined With Irinotecan as Third-line Chemotherapy in Patients With Metastatic Colorectal Cancer - Phase II Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer Metastatic
Keywords: Cancer
Colorectal
Metastatic
Thrid-line
Irinotecan
Cetuximab
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
First posted: 2014-12-15
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: At 2 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: up to 27 months
measure: Disease control rate (DCR)
timeFrame: up to 27 months
measure: Progression-free survival (PFS)
timeFrame: up to 27 months
measure: Duration of response (DOR)
timeFrame: up to 27 months
measure: Time to response (TTR)
timeFrame: up to 27 months
measure: Time to progression (TTP)
timeFrame: up to 27 months
measure: Time to treatment failure (TTF)
timeFrame: up to 27 months
measure: Duration of stable disease (DoSD)
timeFrame: up to 27 months
measure: Overall survival (OS)
timeFrame: up to 27 months
measure: Adverse Events (CTCAE v.4.03)
timeFrame: Up to 27 months
measure: Quality of life
timeFrame: Up to 27 months
measure: Respose rate
timeFrame: up to 27 months
measure: PFS
timeFrame: up to 27 months
Other outcomes:
Locations:
city: Clichy
country: France
facility: Hôpital Beaujon
city: Contamine sur Arve
country: France
facility: Centre hospitalier Alpes Leman
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: La Roche/ Yon
country: France
facility: CHD Vendée
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: Hôpital Européeen
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Nîmes
country: France
facility: CHU Caremeau
city: Paris
country: France
facility: CHU Cochin
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Tenon
city: Saint Brieuc
country: France
facility: Clinique Armoricaine de Radiologie
city: Senlis
country: France
facility: Groupe hospitalier Public du Sud de l'Oise -site de Senlis
city: Strasbourg
country: France
facility: Centre de radiothérapie - Clinique Sainte Anne
city: Suresnes
country: France
facility: Hôpital Foch
city: Thonon les Bains
country: France
facility: Hôpitaux du Léman
city: Tours
country: France
facility: CHU Tours - Hôpital Trousseau
city: Valence
country: France
facility: Clinique Générale
Study officials:
affiliation: Hôpital Saint Louis
name: Jean Marc GORNET, MD
role: PRINCIPAL_INVESTIGATOR
References: