Gemcitabine Alone or in Combination With Other Chemotherapy Drugs in Treating Patients With Metastatic Cancer of the Pancreas

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if gemcitabine is more effective when given alone or in combination with another chemotherapy drug in treating cancer of the pancreas. PURPOSE: Randomized phase II trial to compare the effectiveness of gemcitabine given alone or in combination with other chemotherapy drugs in treating patients who have metastatic cancer of the pancreas.

Detailed Description
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OBJECTIVES: Compare the overall survival rate of patients with metastatic pancreatic cancer treated with gemcitabine alone vs with cisplatin vs with docetaxel vs with irinotecan. Compare the time to disease progression in patients treated with these regimens. Compare the CA 19-9 biomarker response in patients treated with these regimens. Correlate the CA 19-9 biomarker response with survival in patients treated with these regimens. Compare the toxicity of these regimens in these patients. Compare the response in patients with measurable disease treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of four treatment arms. Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 followed by cisplatin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive gemcitabine IV over 150 minutes on days 1, 8, and 15. Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Arm III: Patients receive gemcitabine IV over 30 minutes followed by docetaxel IV over 60 minutes on days 1 and 8. Treatment repeats every 21 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Arm IV: Patients receive gemcitabine IV over 30 minutes followed by irinotecan IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 240 patients (60 per arm) will be accrued for this study within 30 months.

Official Title
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A Randomized Phase II Study Of Gemcitabine/Cisplatin, Gemcitabine/Docetaxel, Gemcitabine/Irinotecan, Or Fixed Dose Rate Infusion Gemcitabine In Patients With Metastic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: docetaxel
* Drug: gemcitabine hydrochloride
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the pancreas Metastatic disease by CT scan PATIENT CHARACTERISTICS: Age: 18 and over Performance status: CTC 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT no greater than 2.5 times upper limit of normal (ULN) Alkaline phosphatase less than 2.5 times ULN if SGOT greater than 1.5 times ULN Alkaline phosphatase any value if SGOT less than 1.5 times ULN Renal: Creatinine no greater than 1.5 mg/dL Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study No other currently active malignancy (completed therapy and considered to be at less than 30% risk of relapse) except non-melanoma skin cancer PRIOR CONCURRENT THERAPY: Chemotherapy: No prior chemotherapy except fluorouracil (5-FU) At least 2 weeks since prior 5-FU No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy except steroids for adrenal failure, hormonal therapy for non-disease related conditions (e.g., insulin for diabetes), or intermittent use of dexamethasone as an antiemetic Radiotherapy: At least 2 weeks since prior radiotherapy No concurrent palliative radiotherapy except whole-brain irradiation for CNS disease

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: Gemcitabine<br>Standard treatment | Drug: gemcitabine hydrochloride<br>* Gemcitabine only arm: 1500 mg/sq m in 250 mL NS IV infusion over 150 min Days 1, 8, & 15 of ea cycle cisplastin arm: 1000 mg/sq m 250 mL NS IV infusion over 30 min Days 1, 8, 15 of ea cycle docetaxel and + irinotecan arms: 1000 mg/sq m in 250 mL NS IV infusion over 30 min Days 1 & 8 of ea cycle<br>|
| Experimental: Gemcitabine + cisplastin<br>Addition of cisplastin to gemcitabine | Drug: cisplatin<br>* 50 mg/sq m IV infusion over 30 min on Days 1 & 15 of ea cycle<br>Drug: gemcitabine hydrochloride<br>* Gemcitabine only arm: 1500 mg/sq m in 250 mL NS IV infusion over 150 min Days 1, 8, & 15 of ea cycle cisplastin arm: 1000 mg/sq m 250 mL NS IV infusion over 30 min Days 1, 8, 15 of ea cycle docetaxel and + irinotecan arms: 1000 mg/sq m in 250 mL NS IV infusion over 30 min Days 1 & 8 of ea cycle<br>|
| Experimental: Gemcitabine + docetaxel<br>Addition of docetaxel to gemcitabine | Drug: docetaxel<br>* 40 mg/sq m IV infusion over 60 min on Days 1 & 8 of ea treatment cycle<br>Drug: gemcitabine hydrochloride<br>* Gemcitabine only arm: 1500 mg/sq m in 250 mL NS IV infusion over 150 min Days 1, 8, & 15 of ea cycle cisplastin arm: 1000 mg/sq m 250 mL NS IV infusion over 30 min Days 1, 8, 15 of ea cycle docetaxel and + irinotecan arms: 1000 mg/sq m in 250 mL NS IV infusion over 30 min Days 1 & 8 of ea cycle<br>|
| Experimental: Gemcitabine + Irinotecan<br>Addition of irinotecan to gemcitabine | Drug: gemcitabine hydrochloride<br>* Gemcitabine only arm: 1500 mg/sq m in 250 mL NS IV infusion over 150 min Days 1, 8, & 15 of ea cycle cisplastin arm: 1000 mg/sq m 250 mL NS IV infusion over 30 min Days 1, 8, 15 of ea cycle docetaxel and + irinotecan arms: 1000 mg/sq m in 250 mL NS IV infusion over 30 min Days 1 & 8 of ea cycle<br>Drug: irinotecan hydrochloride<br>* 100 mg/q m in 500 mL D5W or D5NS IV infusion over 90 min Days 1 & 8 of ea cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 4 years post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression |  | treatment up to 4 years post treatment | 
| Toxicity |  | treatment and up to 4 years post treatment | 

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