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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed 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.

Official Title
-----------------
A Randomized Phase III Study Of Gemcitabine In Combination With Radiation Therapy Versus Gemcitabine Alone In Patients With Localized, Unresectable Pancreatic Cancer

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: Gemcitabine
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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> | Drug: Gemcitabine<br>* Induction: Patients receive the first cycle of gemcitabine 1000 mg/m^2 intravenously once per week for 6 weeks followed by 1 week rest. Consolidation: Following the week of rest, treatment resume with gemcitabine 1000 mg/m^2 administered intravenously once per week for 3 weeks, followed by 1 week rest, for 5 (4-week) cycles.<br>* Other names: Gemzar;|
| Experimental: Gemcitabine + Radiation<br> | Radiation: radiation therapy<br>* Induction: Patients receive gemcitabine 600 mg/m^2 intravenous infusion over 30-60 minutes once a week for 6 weeks while receiving radiation therapy. The first gemcitabine dose is given on the first day of radiation therapy (prior to radiation), then weekly thereafter. All patients on Arm B receive radiation therapy Monday through Friday (no radiation on Saturday or Sunday), weeks 1-6, with once/week gemcitabine. The radiation dose per fraction is 180 cGy prescribed to the isocenter. The total dose of radiation is 5040 cGy given in 28 fractions over 5 1/2 weeks. Consolidation: Additional cycles of gemcitabine begin approximately 4 weeks after completion of radiation therapy.<br>* Other names: Gemzar;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival Time | Overall survival was defined as the time from randomization (registration) to death from any cause. Patients alive at last follow-up were censored. Patients were followed every 3 months for 2 years and then every 6 months for year 3. Patients received treatment beyond 3 years were also followed for survival. | assessed every 3 months for 2 years, then every 6 months for year 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Time | Time from randomization (registration) to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions (taking as reference the baseline sum longest diameter), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Patients were followed every 3 months for 2 years and then every 6 months for year 3. Patients who received treatment beyond 3 years were also followed for survival. | assessed every 3 months for 2 years, then every 6 months for year 3 | 
| Overall Response | Response was assessed per Response Evaluation Criteria In Solid Tumors (RECIST) by CT. Overall response included complete response (CR) and partial response (PR). CR was defined as the disappearance of all target and non-target lesions. PR was defined as CR of target lesions and persistence of one or more non-target lesions or at least a 30% decrease in the sum of the longest diameters of target lesions and non-progressive disease in the non-target lesions. The 71 eligible, treated participants were included in the analysis. | assessed at week 8, and every 3 months for 2 years, then every 6 months for year 3 | 

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