PANIRINOX: Comparison FOLFIRINOX Panitumumab vs mFOLFOX6 Panitumumab in RAS/B-RAF Wild-type Metastatic Colorectal Cancer Patients

Sponsor

UNICANCER (Other)

Overall Status

Recruiting

CT.gov ID

NCT02980510

Collaborator

(none)

209

Enrollment

Locations

Arms

Anticipated Duration (Months)

34.8

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

National trial, multicenter, randomized, phase II assessing FOLFIRINOX + Panitumumab versus mFOLFOX6 + Panitumumab in metastatic colorectal cancer patients selected by RAS and B-RAF status from circulating DNA analysis.

Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan	Phase 2

Detailed Description

PRIMARY OBJECTIVE: Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab

SECONDARY OBJECTIVE(S):

Overall Survival
Progression free survival
Secondary resection
Early tumor shrinkage (ETS)
Depth of response (DpR)
Safety profile (NCI-CTCAE v4.03 classification)
Diagnostic performance of ccfDNA analysis compared to the tumor-tissue analysis (current gold standard)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

209 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab Versus mFOLFOX6 + Panitumumab in Metastatic Colorectal Cancer Patients Selected by RAS and B-RAF Status From Circulating DNA Analysis

Actual Study Start Date :

Dec 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A=Experimental group FOLFIRINOX + Panitumumab oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² given as a 2-hour intravenous (IV) infusion with the addition, after 30 minutes of irinotecan 150 mg/m² given as a 90-minute intravenous infusion through a Y-connector immediately followed by fluorouracil 400 mg/m² IV bolus then 5-fluoruracil (5-FU) 2400 mg/m² over 46 hours continuous infusion.	Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan
Active Comparator: B=Control group mFOLFOX6 + Panitumumab mFOLFOX6 every 2 weeks: oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² IV infusion over 2 hours followed by fluorouracil 400 mg/m² IV bolus then 5-FU 2400 mg/m² over 46 hours continuous infusion.	Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil

Arm

Intervention/Treatment

Experimental: A=Experimental group

FOLFIRINOX + Panitumumab oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² given as a 2-hour intravenous (IV) infusion with the addition, after 30 minutes of irinotecan 150 mg/m² given as a 90-minute intravenous infusion through a Y-connector immediately followed by fluorouracil 400 mg/m² IV bolus then 5-fluoruracil (5-FU) 2400 mg/m² over 46 hours continuous infusion.

Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan

Active Comparator: B=Control group

mFOLFOX6 + Panitumumab mFOLFOX6 every 2 weeks: oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² IV infusion over 2 hours followed by fluorouracil 400 mg/m² IV bolus then 5-FU 2400 mg/m² over 46 hours continuous infusion.

Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil

Outcome Measures

Primary Outcome Measures

Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab. [12 months after inclusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age between 18 and 75 years
ECOG PS between 0 and 1
Histologically confirmed adenocarcinoma of the colon or rectum
Untreated synchronous or metachronous metastatic disease deemed unresectable with curative intent
K-Ras (codons 12, 13, 59, 61, 117, 146), N-Ras (codons 12, 13, 59, 61) and B-Raf (codon 600) wild-type tumor status according to plasma analysis of circulating cell free DNA by Intplex technology
Measurable disease according to RECIST version 1.1
Adequate hematologic, hepatic and renal functions:

Absolute neutrophil count (ANC) ≥2 x 109/L
Haemoglobin ≥9 g/dL
Platelets (PTL) ≥100 x 109/L
AST/ALT ≤5 x ULN
Alkaline phosphatase ≤2.5 x ULN
Bilirubin ≤1.5 x ULN
Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula)

Life expectancy of at least 3 months
Adequate contraception if applicable
Patient affiliated to a social security regimen
Patient information and signed written consent form
Uracilemia < 16 ng/ml

Exclusion Criteria:

History of other malignancy within the previous 5 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)
Adjuvant treatment with oxaliplatin
Previous treatment for metastatic disease
Patients who received any chemo- and/or radiotherapy within 15 days from the date of blood sampling for the RAS and BRAF test
Brain metastases
Patients with a history of severe or life-threatening hypersensitivity to the active substances or to any of the excipients delivered in this study
Patient with history of pulmonary fibrosis or interstitial pneumonitis
Previous organ transplantation, HIV or other immunodeficiency syndromes
Concomitant medications/comorbidities that may prevent the patient from receiving study treatment as uncontrolled intercurrent illness (for instance: active infection, active inflammatory disorders, inflammatory bowel disease, intestinal obstruction, symptomatic congestive heart failure, uncontrolled hypertension…)
Persistent peripheral neuropathy >grade1 (NCI CT v4.03)
Ionic disorders as:

Kalemia ≤1 x LLN
Magnesemia <0.5mmol/L
Calcemia <2mmol/L

Patient with known dihydropyrimidine dehydrogenase deficiency
QT/QTc>450msec for men and >470msec for women
Patient with contraindication for trial drugs (investigators have to refer to SmPC drugs, see Appendix 7)
Concomitant intake of St. John's wort
Other concomitant cancer
Participation in another therapeutic trial
Pregnant woman or lactating woman
Patients with psychological, familial, sociological or geographical condition hampering compliance with the study protocol and follow-up schedule
Legal incapacity or limited legal capacity

Contacts and Locations

Locations

	Site	City	Country
1	Institut Sainte Catherine	Avignon	France
2	Centre Léon Berard	Lyon	France
3	Chu Saint Eloi	Montpellier	France
4	ICM Val D'Aurelle	Montpellier	France
5	Institut de Cancérologie de Lorraine	Nancy	France
6	CHU Carémeau - Institut de Cancérologie du Gard	Nimes	France