Gemcitabine With or Without Exatecan Mesylate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

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 with or without exatecan mesylate in treating pancreatic cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of gemcitabine alone to that of gemcitabine and exatecan mesylate in treating patients who have locally advanced or metastatic pancreatic cancer.

Detailed Description
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OBJECTIVES: Compare the overall survival of patients with chemotherapy-naive locally advanced or metastatic cancer of the exocrine pancreas treated with exatecan mesylate and gemcitabine versus gemcitabine alone. Compare the measures of clinical benefit in patients treated with these regimens. Compare the anti-tumor efficacy of these regimens in this patient population. Determine the safety profile of exatecan mesylate and gemcitabine in these patients. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to performance status (60% vs 70-80% vs 90-100%), extent of disease (locally advanced vs metastatic), and prior radiotherapy for pancreatic cancer (yes or no). Patients are randomized to one of two treatment arms. Arm I: Patients receive exatecan mesylate (DX-8951f) IV over 30 minutes immediately followed by gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive gemcitabine IV over 30 minutes once weekly for up to 7 weeks followed by one week of rest (course 1). For all subsequent courses, patients receive gemcitabine once weekly for 3 weeks followed by one week of rest. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed monthly. PROJECTED ACCRUAL: Approximately 340 patients (170 per treatment arm) will be accrued for this study within 18 months.

Official Title
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A Randomized, Open-Label, Multicenter Phase III Study Comparing the Efficacy and Safety of a Combination of Intravenous DX-8951f (Exatecan Mesylate) Plus Gemcitabine to Gemcitabine Alone in Patients With Locally Advanced or Metastatic Cancer of the Exocrine Pancreas Who Have Not Received Prior Chemotherapy

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: exatecan mesylate
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed epithelial cancer of the exocrine pancreas Locally advanced (unresectable) or metastatic disease No islet cell tumor, lymphoma, or sarcoma of the pancreas No known brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST no greater than 5 times ULN Albumin at least 2.8 g/dL Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No active congestive heart failure No uncontrolled angina No myocardial infarction Other: No serious infection or life-threatening illness unrelated to tumor No other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No overt psychosis or incompetency that would preclude study No history of a positive serology for HIV Not pregnant or nursing Negative pregnancy test Fertile patients must use contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior systemic anticancer immunotherapy for pancreatic cancer No concurrent anticancer immunotherapy or other biologic therapy Chemotherapy: No prior systemic anticancer chemotherapy for pancreatic cancer Prior fluorouracil as a radiosensitizer allowed No prior gemcitabine as a radiosensitizer No other concurrent anticancer chemotherapy Endocrine therapy: Concurrent megestrol for appetite stimulation allowed Radiotherapy: At least 28 days since prior radiotherapy and recovered No prior radiotherapy to more than 25% of estimated bone marrow reserve No concurrent anticancer radiotherapy Surgery: At least 28 days since prior major surgery and recovered No concurrent surgery for cancer Other: No prior investigational or other systemic anticancer therapy for pancreatic cancer No other concurrent investigational drugs

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: exatecan mesylate|nan|
|Drug: gemcitabine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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