Gemcitabine With or Without Radiation Therapy in Treating Patients With Pancreatic Cancer

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 3

Conditions: Pancreatic Cancer

Treatments: Drug: Gemcitabine; Radiation: radiation therapy

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00057876

CDR0000278947

E4201 (Other Identifier)

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether gemcitabine is more effective with or without radiation therapy in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of gemcitabine with or without radiation therapy in treating patients who have locally advanced, unresectable pancreatic cancer.

Full description

OBJECTIVES:

• Compare the overall survival and progression-free of patients with locally advanced, unresectable pancreatic cancer treated with gemcitabine with or without radiotherapy.
• Compare the objective response rate in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the quality of life (QOL) of patients treated with these regimens.
• Determine the effect of gemcitabine and radiotherapy on the QOL of patients with improved objective response rate and progression-free and overall survival.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (0 vs. 1) and weight loss within the past 6 months (less than 10% vs. 10% or more). Patients are randomized to 1 of 2 treatment arms.

Arm I (Gemcitabine alone):

• Induction: Patients receive gemcitabine intravenously (IV) over 30-60 minutes once weekly for 6 weeks followed by 1 week of rest.
• Consolidation: After the 1 week of rest, patients receive gemcitabine IV once weekly for 3 weeks. Treatment repeats every 4 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.

Arm II (Gemcitabine with radiotherapy):

• Induction: Patients receive gemcitabine IV over 30-60 minutes once weekly for 6 weeks beginning on day 1. Patients also undergo concurrent radiotherapy 5 days a week for 5.5 weeks beginning on day 1.
• Consolidation: Approximately 4 weeks after completion of radiotherapy, patients receive gemcitabine IV over 30-60 minutes once weekly for 3 weeks. Treatment repeats every 4 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, week 6, week 15 (for arm II), week 16 (for arm I), and 9 months.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year. Patients who receive treatment beyond 3 years are followed for survival.

ACCRUAL: 74 patients were accrued for this study.

Enrollment: 74 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

  • Locally advanced or regional (encompassable within the same radiotherapy portals)
  • Adenosquamous cancers are allowed

• Unresectable disease

• Measurable and/or non-measurable disease as determined by computed tomography (CT) scan or magnetic resonance imaging (MRI), which must be performed within 4 weeks prior to randomization.

• Age>=18

• ECOG Performance status of 0-1

• Life expectancy >= 12 weeks

• Adequate bone marrow reserve,liver and renal function within 2 weeks of randomization:

  • Absolute granulocyte count at least 2,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin less than 3 mg/dL (unless secondary to biliary obstruction or cholangitis)
  • Serum glutamic-oxaloacetic (AST) less than 5 times upper limit of normal (ULN)
  • Albumin greater than 2.5 g/dL
  • Creatinine no greater than 1.5 times ULN

• Fertile patients must use effective contraception

• Willing and able to attend follow-up visits

• Concurrent enrollment on protocol ECOG-E1Y03 allowed

• More than 4 weeks since prior investigational agents

Exclusion criteria

• Candidate for surgical excision based on local extent of disease (e.g., T3, N1, M0)
• Stage M1 disease
• Small cell, mucinous cystadenocarcinoma, islet cell or papillary cystic histology
• Pregnant or nursing
• Active infection within within 4 weeks of randomization
• Malignancy within the past 5 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or organ-confined prostate cancer (Gleason score no greater than 7)
• History of active collagen vascular disease (i.e., systemic lupus erythematosus, rheumatoid arthritis, or scleroderma)
• Signs or symptoms of peptic or duodenal ulcer disease
• Concurrent serious systemic disorders that are incompatible with study participation
• Prior chemotherapy for pancreatic cancer
• Prior radiotherapy
• Concurrent intensity modulated radiotherapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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74 participants in 2 patient groups

Gemcitabine

Active Comparator group

Treatment:

Drug: Gemcitabine

Gemcitabine + Radiation

Experimental group

Treatment:

Radiation: radiation therapy