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

Daiichi Sankyo

Status and phase: Completed; Phase 3

Conditions: Pancreatic Cancer

Treatments: Drug: exatecan mesylate; Drug: gemcitabine hydrochloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT00023972

DAIICHI-8951A-PRT031

MSKCC-02011

CDR0000068880

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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