A Randomized Phase III Trial Comparing Folfirinox to Gemcitabine in Locally Advanced Pancreatic Carcinoma (NEOPAN)

Unicancer

Status and phase: Completed; Phase 3

Conditions: Carcinoma; Pancreatic Cancer

Treatments: Drug: Folinic Acid; Drug: Oxaliplatin; Drug: Irinotecan; Drug: 5-Fluoro-uracil; Drug: Gemcitabine; Drug: L-folinic

Study type: Interventional

Funder types: Other

Identifiers

NCT02539537

PRODIGE 29 (UCGI 26)

2014-003510-82 (EudraCT Number)

Details and patient eligibility

About

French national multicentric phase III trial evaluating chemotherapy with Folfirinox or gemcitabine in locally advanced pancreatic carcinoma.

Full description

Comparative interventional prospective phase 3, randomized, open-label, multicentric trial comparing chemotherapy with Folfirinox to Gemcitabine in locally advanced pancreatic carcinoma.

Enrollment: 171 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically or cytologically confirmed adenocarcinoma of the pancreas

2. Proven unresectability after multidisciplinary discussion involving radiologist and a surgeon

3. Locally advanced (i.e.: no metastasis or suspicion of metastasis) and unresectable tumors: for example mesenteric or portal vein involvement, or > 180° encasement of the superior mesenteric artery, or celiac abutment (NCCN 2012 criteria)

4. Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST 1.1

5. WHO Performance status (PS) 0-1

6. Age ≥18 years

7. Patient with organ function as follows:

   • Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
   • Hemoglobin ≥ 10 g/dL
   • Platelets (PTL) ≥ 75 x 10⁹/L
   • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
   • Bilirubin ≤ 1.5 x ULN
   • Creatinine ≤ 2 x ULN
   • Albumin > 0.75 x lower limit of normal (LLN)
   • Urea ≤ 2 x ULN

8. Adequate vital functions

9. Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use medically acceptable methods of contraception during the study and for 4 months after the last intake of study treatment for women and for 6 months after for men.

10. Patient information and signed informed consent form

11. Public or private health insurance coverage

12. Uracilemia < 16 ng/ml

Exclusion criteria

1. Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or in situ cervical cancer
2. Patient with metastasis or with history of metastasis
3. Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline)
4. Major comorbidity, active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes that may preclude the delivery of the treatment
5. Pre-existing neuropathy (Grade ≥ 2), Gilbert's disease or genotype UGT1A1 * 28 / * 28
6. Pregnant woman
7. Fructose intolerance
8. Patients currently treated by warfarin
9. Persons deprived of liberty or under guardianship
10. Psychological condition, family-, sociological- or geographical situation potentially hampering compliance with the study protocol and the follow-up schedule

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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171 participants in 2 patient groups

Arm A: Gemcitabine

Active Comparator group

Description:

Gemcitabine 1000 mg/m² IV infusion over 30 minutes on D1 of each week for the 4 weeks of the first cycle (1 cycle = 4 weeks). For the following five cycles, gemcitabine infusion on D1, D8, and D15 of each cycle, followed by 1 week without injection (i.e. in total 4 cycles over 24 weeks; with 19 administrations of Gemcitabine).

Treatment:

Drug: Gemcitabine

Arm B: Folfirinox

Experimental group

Description:

Administered once every 14 days for 24 weeks (12 cycles). A cycle equals 14 days with injection on D1 of each cycle. Treatment starts with oxaliplatin (85 mg/m²) administration; IV infusion over 2 hours, followed by the simultaneous administration (using a Y-tubing) of folinic acid 400 mg/m² (racemic) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours and irinotecan 180 mg/m² IV infusion over 90 minutes. The irinotecan will begin 30 minutes after the start of the folinic acid infusion. 5-Fluoro-uracil (5-FU) IV 2,400 mg/m²/h will be administered over 46 hours after the end of the folinic acid infusion, i.e. 1200 mg/m²/day for the duration of 2 days. Treatment will be continued for 24 weeks (12 cycles).

Treatment:

Drug: L-folinic

Drug: 5-Fluoro-uracil

Drug: Folinic Acid

Drug: Irinotecan

Drug: Oxaliplatin