Combination Chemotherapy in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them in different ways may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating metastatic pancreatic cancer. PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work in treating patients with metastatic pancreatic cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Compare the overall survival of patients with unresectable metastatic pancreatic cancer treated with fluorouracil, leucovorin calcium, and cisplatin followed by gemcitabine hydrochloride vs gemcitabine hydrochloride followed by fluorouracil, leucovorin calcium, and cisplatin. Secondary Compare progression-free survival of patients treated with these regimens. Compare the toxicity of these regimens in these patients. Compare the quality of life of patients treated with these regimens. Compare the percentage of these patients needing second-line therapy. Compare the duration of hospitalization of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 or 1 vs 2), participating center, location of the tumor (ampullar region vs other locations), and infusion rate of gemcitabine hydrochloride (30 vs 100 minutes). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive leucovorin calcium IV over 2 hours on day 1, cisplatin IV over 1 hour on day 1 or 2, and fluorouracil IV over 46 hours on day 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease progression also receive gemcitabine hydrochloride IV over 30 or 100 minutes weekly for 7 weeks. Patients then receive gemcitabine hydrochloride IV on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive gemcitabine hydrochloride IV over 30 or 100 minutes weekly for 7 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease progression receive fluorouracil, leucovorin calcium, and cisplatin as in arm I. Quality of life is assessed at baseline and then every 2 months. After completion of study therapy, patients are followed periodically for 2 years. PROJECTED ACCRUAL: A total of 202 patients will be accrued for this study.

Official Title
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Essai Randomise Comparant Deux Stategies De Chimiotherapie Dans Les Cancers Pancreatiques Avances: LV5FU2 Simplifie + Cisplatine Suivi de Gemcitabine, Versus Gemcitabine Suivi de LV5FU2 Simplifie + Cisplatine en Can de Progression

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: fluorouracil
* Drug: gemcitabine hydrochloride
* Drug: leucovorin calcium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the pancreas or ampulla Metastatic disease Unresectable disease Measurable disease, meeting the following criteria: No prior radiotherapy to the only site of measurable disease Diameter > 10 mm by spiral CT scan or MRI OR > 20 mm by conventional methods No brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 2 months No contraindication to chemotherapy Creatinine clearance > 60 mL/min Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Alkaline phosphatase < 5 times normal Bilirubin ≤ 3 mg/dL No coronary insufficiency No symptomatic cardiac disease Good hydration possible No Child-Pugh class B or C cirrhosis No other malignancy except for basal cell skin cancer or carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior palliative or adjuvant chemotherapy At least 4 weeks since prior radiotherapy No radiotherapy during or for 4 weeks after study therapy No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: LV5FU2 simplifié + cisplatine puis gemcitabine si progression<br>LV5FU2 simplifié + cisplatine puis gemcitabine si progression | Drug: cisplatin<br> <br> Drug: fluorouracil<br> <br> Drug: gemcitabine hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> |
| Experimental: gemcitabine puis LV5FU2 simplifié + cisplatine si progression<br>gemcitabine puis LV5FU2 simplifié + cisplatine si progression | Drug: cisplatin<br> <br> Drug: fluorouracil<br> <br> Drug: gemcitabine hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 2012 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 2012 | 
| Toxicity |  | 2012 | 
| Quality of life |  | 2012 | 
| Percentage of patients needing second-line therapy |  | 2012 | 
| Duration of hospitalization |  | 2012 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the pancreas, recurrent pancreatic cancer, stage IV pancreatic cancer