FIrst Line Treatment of Metastatic Pancreatic Cancer: Sequential Nab-paclitaxel + Gemcitabine/FOLFIRI.3 VS Nab-paclitaxel + Gemcitabine

Study Overview
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Brief Summary
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The main objective of this trial is to evaluate every 2 months alternating nab-paclitaxel/gemcitabine and FOLFIRI.3 versus nab-paclitaxel + gemcitabine, regarding the progression of disease at 6 months.

Official Title
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Phase II Randomised Multicenter Trial Evaluating a Sequential Treatment With Nab-paclitaxel+Gemcitabine /FOLFIRI.3 vs Nab-paclitaxel + Gemcitabine in First Line Metastatic Pancreatic Cancer

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: FOLFIRI.3
* Drug: nab-paclitaxel+ gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological confirmation of pancreatic adenocarcinoma Distant metastatic disease Scan (or MRI if scanner contraindicated) completed within 3 weeks of the start of treatment At least one lesion measurable by RECIST v1.1 criteria Life expectancy> 3 months No previous chemotherapy (adjuvant chemotherapy with gemcitabine authorised if administered more than 6 months prior to inclusion) No previous radiotherapy (unless at least one measurable target lesion outside the irradiation zone) Pain must be monitored before inclusion 18 years < age < 75 Performance status: WHO < 2 ANC ≥ 1500/mm3, platelets ≥ 100 000/mm3, haemoglobin ≥ 9 g/dL ASAT (SGOT), ALAT (SGPT) ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases found Bilirubin ≤ 1.5 x ULN (patients drained by retrograde technique are includable), creatinine < 120 μmol/L, or MDRD creatinine clearance > 60 mL/min Women of childbearing age must have a negative pregnancy test (β HCG) before starting treatment Women of childbearing age as well as men (who have sexual intercourse with women of childbearing age) must agree to use effective contraception without interruption for the duration of treatment and 6 months after the administration of the last treatment dose Patient affiliated to the social security scheme Patient information and signature of informed consent Exclusion Criteria: - Other types of pancreatic tumours, especially endocrine or acinar cell tumours Ampulloma Presence of meningeal or cerebral metastases, bone metastases Gilbert's syndrome Presence of neuropathy> grade 1 according to NCIC-CTC 4.0 Contraindications specific to the studied treatments History of chronic diarrhoea or inflammatory disease of the colon or rectum, or of unresolved occlusion or sub-occlusion for which symptomatic treatment is being administered Other concomitant cancer or history of cancer during the 5 years, with the exception of a carcinoma in situ of the cervix or basal cell or squamous cell carcinoma, considered cured Significant history of heart or respiratory disease, including any history of interstitial pneumonia Patient already included in another clinical trial with an experimental molecule Women who are breast-feeding Persons deprived of liberty or under guardianship Unable to submit to medical monitoring during the trial due to geographical, social or psychological reasons

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nab-paclitaxel + gemcitabine/FOLFIRI.3<br>Alternance of : 2 months with nab-paclitaxel (125 g/m² - 30 min in IV) + gemcitabine (1000 mg/m², 30 min in IV, 3 injections follow by 1 week free) follow by 2 months with FOLFIRI.3 (irinotecan: 90 mg/m² at D1, acid folinic 400 mg/m², 5Fu continus: 2000 mg/m² IV 46 hours, and irinotecan at D3, 90 mg/m²) This alternance continus until progression | Drug: FOLFIRI.3<br>* For each cycle : 1 week out of 2 - injection at Day1, J15 Irinotécan 90 mg/m² at day1 in perfusion over 60 min in Y of folinic acid Folinic Acid 400 mg/m² (or 200 mg/m² Elvorine) at Day 1 in perfusion over 2 hours 5FU continu 2000 mg/m² during 46 hours Irinotécan at 90 mg/m² in perfusion over 60 mn at Day 3 (when 5FU perfusion is over)<br>Drug: nab-paclitaxel+ gemcitabine<br>* For each cycle : 3 weeks out of 4 - injection at Day 1, 8 and 15 Nab-paclitaxel : 125 mg/m² of nab-paclitaxel in perfusion over 30 mn. Gemcitabine 1000 mg/m² in perfusion over 30 mn immediately after Nab paclitaxel administration is over.<br>|
| Active Comparator: nab-paclitaxel + gemcitabine<br>nab-paclitaxel (125 g/m² - 30 min in IV) + gemcitabine (1000 mg/m² - 30 min in IV) 3 injections follow by 1 week free, until progression | Drug: nab-paclitaxel+ gemcitabine<br>* For each cycle : 3 weeks out of 4 - injection at Day 1, 8 and 15 Nab-paclitaxel : 125 mg/m² of nab-paclitaxel in perfusion over 30 mn. Gemcitabine 1000 mg/m² in perfusion over 30 mn immediately after Nab paclitaxel administration is over.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients alive without progression 6 months after inclusion | The progression is clinically and/or radiologically assessed by the investigator (as defined in 1.1) according to RECIST v1.1 criteria. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS): | Time interval between the randomisation date and the date of death (all causes). The patients alive will be censored at the end-point or the date of the latest event | 1 and 2 years | 
| Objective response rate (ORR) | Complete or partial response rates in imaging by RECIST v1.1 over the entire treatment period according the investigator | 6 months | 
| Progression-free survival: | Time interval between the randomisation date and the date of first progression (clinical and/or radiological) or death (whatever the cause). Living patients without progression will be censored at the end-point or date of latest event. | 1 and 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer