Back to resultsComparison FOLFIRINOX Panitumumab vs mFOLFOX6 Panitumumab in RAS/B-RAF Wild-type Metastatic Colorectal Cancer Patients (PANIRINOX)
Primary Purpose
Metastatic Colorectal Cancer
Status
Active
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil
Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
Eligibility Criteria
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
Sites / Locations
- Institut Sainte Catherine
- Centre Léon Berard
- Chu Saint Eloi
- ICM Val D'Aurelle
- Institut de Cancérologie de Lorraine
- CHU Carémeau - Institut de Cancérologie du Gard
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
A=Experimental group
B=Control group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02980510
Brief Title
Comparison FOLFIRINOX Panitumumab vs mFOLFOX6 Panitumumab in RAS/B-RAF Wild-type Metastatic Colorectal Cancer Patients
Acronym
PANIRINOX
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2016 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
None (Open Label)
Masking Description
The primary endpoint is the complete response rate where complete response is defined as complete disappearance of metastatic lesions after a maximum of 12 cycles of chemotherapy and tumor marker level normalization (CEA).
Allocation
Randomized
Enrollment
219 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A=Experimental group
Arm Type
Experimental
Arm Description
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.
Arm Title
B=Control group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil
Intervention Type
Drug
Intervention Name(s)
Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan
Primary Outcome Measure Information:
Title
Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.
Time Frame
12 months after inclusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thibault MAZARD
Organizational Affiliation
ICM VAL D'AURELLE
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Sainte Catherine
City
Avignon
Country
France
Facility Name
Centre Léon Berard
City
Lyon
Country
France
Facility Name
Chu Saint Eloi
City
Montpellier
Country
France
Facility Name
ICM Val D'Aurelle
City
Montpellier
Country
France
Facility Name
Institut de Cancérologie de Lorraine
City
Nancy
Country
France
Facility Name
CHU Carémeau - Institut de Cancérologie du Gard
City
Nimes
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Comparison FOLFIRINOX Panitumumab vs mFOLFOX6 Panitumumab in RAS/B-RAF Wild-type Metastatic Colorectal Cancer Patients
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