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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Jun 2017 → ongoing

Decision date (initial)

2024-03-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AMGEN

External identifiers

EU CT number

2024-510645-34-00

EudraCT number

2016-001490-33

ClinicalTrials.gov

NCT02980510

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab

Secondary objectives 7

1. Overall Survival
2. Progression free survival
3. Secondary resection
4. Early tumor shrinkage (ETS)
5. Depth of response (DpR)
6. Safety profile (NCI CTCAE v 4.03 classification)
7. Diagnostic performance of ccfDNA analysis compared to the tumor-tissue analysis (current gold standard)

Conditions and MedDRA coding

RAS and B-RAF wild-type metastatic colorectal cancer. RAS and B-RAF mutation will be determined using circulating cell-free DNA (ccfDNA) by IntPlex method

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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 20

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete response rate where complete response is defined as complete disappearance of metastatic lesions after maximum of 12 cycles of chemotherapy and tumor marker level normalization (CEA). Complete disappearance of metastatic lesions will be assessed according to RECIST criteria version 1.1: Disappearance of all target and non-target lesions on the same method of assessment that at baseline (CT Scan or MRI). Every complete response will have to be confirmed 4 to 6 weeks after the last trt

Secondary endpoints 7

1. Overall Survival (OS) is defined as the time from the date of randomization to the date of documented death from any cause
2. Progression-Free Survival (PFS) is defined as the time from the date of randomization to the date of documented progression or any cause of death. Progression will be assessed by CT scan or MRI according to RECIST criteria version 1.1
3. Secondary resection rate is defined as the percentage of patients with initially irresectable metastases who will have a secondary resection R0 or R1 of their metastases
4. Early tumor shrinkage (ETS) is defined as the relative change in the sum of longest diameters of RECIST target lesions after 4 cycles compared to baseline
5. Depth of response (DpR) is defined as the relative change in the sum of longest diameters of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, as compared to baseline
6. Adverse events rate will be graded based on NCI CTCAE v4.03 classification
7. Diagnostic performance of ccfDNA analysis compared to the tumor-tissue analysis (current gold standard)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Director of regulatory Affairs and Pharmacovigilance

Public contact point

Organisation

Unicancer

Contact name

Director of regulatory Affairs and Pharmacovigilance

Locations

1 EU/EEA country · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications