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.
Recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil | B=Control group | |
| Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan | A=Experimental group |
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)
| Name | Type | Description | Interventions |
|---|---|---|---|
| A=Experimental group | Experimental | 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. |
|
| B=Control group | Active Comparator | 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. |
|
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
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab. |
| Time Frame: | 12 months after inclusion |
| Safety Issue: | |
| Description: |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | UNICANCER |
July 21, 2021
