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

Federation Francophone de Cancerologie Digestive

Status and phase: Completed; Phase 3

Conditions: Pancreatic Cancer

Treatments: Drug: fluorouracil; Drug: gemcitabine hydrochloride; Drug: cisplatin; Drug: leucovorin calcium

Study type: Interventional

Funder types: Other

Identifiers

NCT00303758

FFCD-0301

CDR0000453841

EU-20543

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 202 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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202 participants in 2 patient groups

LV5FU2 simplifié + cisplatine puis gemcitabine si progression

Active Comparator group

Description:

LV5FU2 simplifié + cisplatine puis gemcitabine si progression

Treatment:

Drug: leucovorin calcium

Drug: fluorouracil

Drug: gemcitabine hydrochloride

Drug: cisplatin

gemcitabine puis LV5FU2 simplifié + cisplatine si progression

Experimental group

Description:

gemcitabine puis LV5FU2 simplifié + cisplatine si progression

Treatment:

Drug: leucovorin calcium

Drug: fluorouracil

Drug: gemcitabine hydrochloride

Drug: cisplatin