Gemcitabine With Or Without Radiation Therapy In Treating Patients With Pancreatic Cancer

Study Overview

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

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.

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.

Pancreatic Cancer

DRUG: Gemcitabine
RADIATION: radiation therapy

CDR0000278947
U10CA021115 (U.S. NIH Grant/Contract)
E4201 (OTHER Identifier) (OTHER: Eastern Cooperative Oncology Group (ECOG) and Radiation Therapy Oncology Group (RTOG))

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2003-04-07	Results First Submitted 2011-02-28	Last Update Submitted that met QC Criteria 2023-06-20
First Submitted that Met QC Criteria 2003-04-08	Results First Submitted that Met QC Criteria 2011-02-28	Last Update Posted (ACTUAL) 2023-07-05
First Posted (ACTUAL) 2003-04-09	Results First Posted 2011-03-25	Last Verified 2023-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: Gemcitabine	DRUG: Gemcitabine 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 on RADIATION: radiation therapy 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 week
EXPERIMENTAL: Gemcitabine + Radiation	RADIATION: radiation therapy 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 week

Participant Group/Arm

Intervention/Treatment

ACTIVE_COMPARATOR: Gemcitabine

DRUG: Gemcitabine

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 on

RADIATION: radiation therapy

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 week

EXPERIMENTAL: Gemcitabine + Radiation

RADIATION: radiation therapy

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 week

Primary Outcome Measures	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	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)
Radiation Therapy Oncology Group

Investigators

STUDY_CHAIR: Patrick J. Loehrer, MD, Indiana University Melvin and Bren Simon Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Loehrer PJ, Powell ME, Cardenes HR, et al.: A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer: E4201. [Abstract] J Clin Oncol 26 (Suppl 15): A-4506, 2008.

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Clinical Trial Record