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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan; Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil

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 Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Avignon, France
    • Institut Sainte Catherine
  • Lyon, France
    • Centre Léon Bérard
  • Montpellier, France
    • ICM Val d'Aurelle
  • Montpellier, France
    • Chu Saint Eloi
  • Nancy, France
    • Institut de Cancerologie de Lorraine
  • Nimes, France
    • CHU Carémeau - Institut de Cancérologie du Gard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18 and 75 years
2. ECOG PS between 0 and 1
3. Histologically confirmed adenocarcinoma of the colon or rectum
4. Untreated synchronous or metachronous metastatic disease deemed unresectable with curative intent
5. 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
6. Measurable disease according to RECIST version 1.1

7. 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)
8. Life expectancy of at least 3 months
9. Adequate contraception if applicable
10. Patient affiliated to a social security regimen
11. Patient information and signed written consent form
12. Uracilemia < 16 ng/ml

Exclusion Criteria:

1. History of other malignancy within the previous 5 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)
2. Adjuvant treatment with oxaliplatin
3. Previous treatment for metastatic disease
4. Patients who received any chemo- and/or radiotherapy within 15 days from the date of blood sampling for the RAS and BRAF test
5. Brain metastases
6. Patients with a history of severe or life-threatening hypersensitivity to the active substances or to any of the excipients delivered in this study
7. Patient with history of pulmonary fibrosis or interstitial pneumonitis
8. Previous organ transplantation, HIV or other immunodeficiency syndromes
9. 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…)
10. Persistent peripheral neuropathy >grade1 (NCI CT v4.03)

11. Ionic disorders as:

    • Kalemia ≤1 x LLN
    • Magnesemia <0.5mmol/L
    • Calcemia <2mmol/L
12. Patient with known dihydropyrimidine dehydrogenase deficiency
13. QT/QTc>450msec for men and >470msec for women
14. Patient with contraindication for trial drugs (investigators have to refer to SmPC drugs, see Appendix 7)
15. Concomitant intake of St. John's wort
16. Other concomitant cancer
17. Participation in another therapeutic trial
18. Pregnant woman or lactating woman
19. Patients with psychological, familial, sociological or geographical condition hampering compliance with the study protocol and follow-up schedule
20. Legal incapacity or limited legal capacity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.	12 months after inclusion

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Principal Investigator: Thibault MAZARD, ICM Val d'Aurelle

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: December 1, 2016
• First Posted (Estimated): December 2, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Micronutrients; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Protective Agents; Antidotes; Vitamin B Complex; Vitamins; Hematinics; Oxaliplatin; Irinotecan; Panitumumab; Fluorouracil; Leucovorin; Levoleucovorin; Folic Acid
• Other Study ID Numbers: UCGI 28 PANIRINOX; 2016-001490-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
• IPD Sharing Time Frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
• IPD Sharing Access Criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No