Randomized Multicenter Phase II/III Study With Adjuvant Gemcitabine Versus Neoadjuvant / Adjuvant FOLFIRINOX for Resectable Pancreas Carcinoma

Phase 2

Completed

• Conditions: Resectable Prancreas Carcinoma
• Interventions: Drug: Oxaliplatin; Drug: Gemcitabine; Drug: 5-Fluorouracil; Drug: Irinotecan; Drug: Natriumfolinate

• Registration Number: NCT02172976
• Lead Sponsor: Krankenhaus Nordwest

Brief Summary

In this multicenter study, patients with resectable pancreatic carcinoma will be treated with (a) surgery followed by 6 cycles gemcitabine or (b) 4-6 cycles FOLFIRINOX followed by surgery followed by 4-6 cycles FOLFIRINOX.

The overall survival between both therapies will be compared as well as other parameters.

Detailed Description

This is a phase II/III randomized multicenter study. Patients with resectable pancreatic carcinoma will be randomized in Arm A (surgery plus adjuvant gemcitabine, 6 cycles) or Arm B (4-6 cycles FOLFIRINOX neoadjuvant, 4-6 cycles FOLFIRINOX adjuvant).

Primary endpoint is the overall survival, secondary endpoints are progression-free survival, perioperative morbidity and mortality, rate of R0 resections, tolerability and feasibility of neoadjuvant FOLFIRINOX and others.

Study Timeline

• Study First Submitted: 2014-05-23
• Study First Submitted QC: 2014-06-23
• Study First Posted: 2014-06-24
• Study Start: 2014-11
• Primary Completion: 2020-01
• Study Completion: 2020-05
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-01
• Last Update Posted: 2020-09-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Histologically confirmed adenocarcinoma of the pankreas. For histological confirmation, max. 3 tests are allowed. If no confirmation of carcinoma is possible, the patient can not be included into the study.
2. Radiological confirmation of a locally limited curativ resectable (primarily resectale or borderline situation) pankreas carcinoma without distant metastases.
3. no prior pancreas resection
4. no prior cytostatic chemotherapy
5. female and male patients > 18 and <=75 years using contraception
6. ECOG ≤ 1
7. medical resectability
8. granulocytes > 1.500/µl
9. thrombocytes > 100.000/µl
10. hemoglobin ≥ 8,0 g/dl
11. serumcreatinine ≤ 1.5x of normal value or Creatinine-Clearance > 50 ml/min
12. written informed consent

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Exclusion Criteria

1. Endocrine pancreas carcinoma
2. locally advanced inoperable stages: non-resectable infiltration of V. porta or longway infiltration of A. mesenterica superior or infiltration of Truncus coeliacus.
3. distant metastases
4. Relapse
5. prior radiotherapy of measurable lesions
6. peritonealcarcinosis
7. malignant secondary disease, dated back < 5 years (exeption: in-situ-carcinoma of the cervix, adequately treated skin basal cell carcinoma)
8. contraindication for operative resection
9. ECOG ≥ 2
10. severe liver dysfunction (AST/ALT>3,5xULN, AP>6xULN)
11. Transhepatic drainage
12. active CHD (symptoms present), cardiomyopathy or heart insufficiency stage III-IV according to NYHA and EF < 45%
13. severe non-surgical accompanying diseases or acute infection
14. chronic diarrhea
15. chronic inflammable gastro-intestinal disease
16. peripheral polyneuropathy > NCI grade II
17. pregnancy or lactation
18. hypersensibility or contraindication for Gemcitabine, Oxaliplatin, Natriumfolinate, Irinotecan or 5-Fluorouracil
19. participation in another interventional trial

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FOLFIRINOX	Oxaliplatin	Oxaliplatin 85mg/m², Irinotecan 180mg/m², 5-FU 400mg/m² Bolus i.v., 5-FU continuous Infusion 2400 mg/m² Natriumfolinate 400mg/m² 46h d1; qd15 6 cycles pre- and 6 cycles post- surgery
FOLFIRINOX	5-Fluorouracil	Oxaliplatin 85mg/m², Irinotecan 180mg/m², 5-FU 400mg/m² Bolus i.v., 5-FU continuous Infusion 2400 mg/m² Natriumfolinate 400mg/m² 46h d1; qd15 6 cycles pre- and 6 cycles post- surgery
FOLFIRINOX	Irinotecan	Oxaliplatin 85mg/m², Irinotecan 180mg/m², 5-FU 400mg/m² Bolus i.v., 5-FU continuous Infusion 2400 mg/m² Natriumfolinate 400mg/m² 46h d1; qd15 6 cycles pre- and 6 cycles post- surgery
FOLFIRINOX	Natriumfolinate	Oxaliplatin 85mg/m², Irinotecan 180mg/m², 5-FU 400mg/m² Bolus i.v., 5-FU continuous Infusion 2400 mg/m² Natriumfolinate 400mg/m² 46h d1; qd15 6 cycles pre- and 6 cycles post- surgery
Gemcitabine	Gemcitabine	Gemcitabine 1000 mg/m² d1, d8, d15; qd 29; 6 cycles after surgery

Primary Outcome Measures

Name	Time	Method
median overall survival	From date of randomization until the date of death from any cause assessed up to 24 months

Secondary Outcome Measures

Name	Time	Method
median progression-free survival (PFS)	From date of randomization until the date of first documented progression / relapse or date of death from any cause, whichever came first, assessed up to 24 months
perioperative morbidity and mortality	30 days after surgery
R0 resection rate	2 months after surgery
adverse events (grade, number per patient) related to of G-CSF prophylaxis in the Folfirinox arm	up to 40 weeks
pathological complete remission	at surgery	during surgery, paraffin embedded tissue is prepared for analysis which is analyzed for remission grading at the central pathology afterwards
prevalence of iron deficiency	baseline, d1 of every cycle, end of treatment

Trial Locations

Locations (1)

Institute of Clinical Cancer Research (IKF), UCT - University Cancer Center, Frankfurt, Germany; 🇩🇪 Frankfurt, Germany