Gemcitabine With or Without Radiation Therapy in Treating Patients With Pancreatic Cancer - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborators:	National Cancer Institute (NCI) Radiation Therapy Oncology Group
Information provided by:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00057876

Purpose

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.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: Gemcitabine Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomized Phase III Study Of Gemcitabine In Combination With Radiation Therapy Versus Gemcitabine Alone In Patients With Localized, Unresectable Pancreatic Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:

Overall Survival Time [ Time Frame: assessed every 3 months for 2 years, then every 6 months for year 3 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Progression-free Survival Time [ Time Frame: assessed every 3 months for 2 years, then every 6 months for year 3 ] [ Designated as safety issue: No ]
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.
Overall Response [ Time Frame: assessed at week 8, and every 3 months for 2 years, then every 6 months for year 3 ] [ Designated as safety issue: No ]
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.

Enrollment:	74
Study Start Date:	April 2003
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 once per week for 3 weeks, followed by 1 week rest, for 5 (4-week) cycles. Other Names: 2-Deoxy-2 2-difluorocytidine monohydrochloride Gemzar
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 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. Other Names: 2-Deoxy-2 2-difluorocytidine monohydrochloride Gemzar

Arms

Assigned Interventions

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 once per week for 3 weeks, followed by 1 week rest, for 5 (4-week) cycles.

Other Names:

2-Deoxy-2
2-difluorocytidine monohydrochloride
Gemzar

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 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.

Other Names:

2-Deoxy-2
2-difluorocytidine monohydrochloride
Gemzar

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 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00057876

Show 229 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Radiation Therapy Oncology Group

Investigators

Study Chair:

Patrick J. Loehrer, MD

Indiana University Melvin and Bren Simon Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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.

Responsible Party:	Robert Comis, M.D., ECOG Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00057876 History of Changes
Other Study ID Numbers:	CDR0000278947, U10CA021115, E4201
Study First Received:	April 7, 2003
Results First Received:	February 28, 2011
Last Updated:	June 21, 2011
Health Authority:	United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:

stage III pancreatic cancer
adenocarcinoma of the pancreas

Additional relevant MeSH terms:

Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on February 09, 2012