Clinical trial NCT00058149: Gemcitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Official title: A Phase III, Randomized Study of Gemcitabine (Fixed-Dose Rate Infusion) and Oxaliplatin (NSC 266046) Versus Gemcitabine (Fixed-Dose Rate Infusion) Versus Gemcitabine (30-Minute Infusion) in Pancreatic Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: stage II pancreatic cancer
stage III pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-04-09
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy such as gemcitabine and oxaliplatin use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways may kill more tumor cells. It is not yet known whether gemcitabine is more effective with or without oxaliplatin in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of gemcitabine with or without oxaliplatin in treating patients who have locally advanced or metastatic pancreatic cancer.

Detailed description: OBJECTIVES:

* Compare survival of patients with locally advanced or metastatic pancreatic cancer treated with prolonged infusion gemcitabine with vs without oxaliplatin vs standard infusion gemcitabine.
* Compare the toxicity of these regimens in these patients.
* Compare the objective response in patients treated with these regimens.
* Compare the patterns of failure and progression-free survival of patients treated with these regimens.
* Compare the reported frequency of deep vein thrombosis and pulmonary embolism among patients treated with these regimens.
* Compare the changes in quality of life, including improved symptom control and/or additional side effects of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 or 1 vs 2) and disease stage (locally advanced vs metastatic). Patients are randomized to 1 of 3 treatment arms.

* Arm I (standard treatment): Patients receive gemcitabine IV over 30 minutes once weekly for 7 weeks followed by 1 week of rest for course 1 only. In all subsequent courses, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15, with courses repeating every 4 weeks in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive gemcitabine IV over 150 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
* Arm III: Patients receive gemcitabine IV over 100 minutes on day 1 and oxaliplatin IV over 120 minutes on day 2. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then at 8 and 16 weeks.

Patients are followed for 3 years.

PROJECTED ACCRUAL: A total of 789 patients (263 per treatment arm) will be accrued for this study within 18 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma or poorly differentiated carcinoma
* Ineligible for curative resection
* Measurable and/or nonmeasurable disease
* Must have evidence of disease outside prior radiation fields OR radiologically confirmed progression of disease within the radiation fields after completion of radiotherapy

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* WBC ≥ 3,500/mm\^3 OR
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 125,000/mm\^3

Hepatic

* Bilirubin \< 2.0 mg/dL
* AST \< 3 times upper limit of normal (ULN)

Renal

* Creatinine ≤ 1.5 times ULN

Cardiovascular

* No uncontrolled cardiac disease

Other

* Not pregnant or nursing
* Negative pregnancy test

  * Negative vaginal ultrasound for patients with an elevated beta human chorionic gonadotropin level
* Fertile patients must use effective nonhormonal contraception
* No other malignancies within the past 5 years except nonmetastatic, nonmelanoma skin cancer, carcinoma in situ of the cervix, or cancer cured by surgery or small field radiotherapy
* No active or uncontrolled infection
* No other active illness that would preclude study participation
* No symptomatic sensory peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy for metastatic disease
* No prior (including adjuvant) gemcitabine or oxaliplatin
* Prior adjuvant chemotherapy allowed provided there was more than 6 months between the last dose of adjuvant chemotherapy and recurrence of pancreatic cancer
* Prior chemotherapy as a radiosensitizing agent allowed\* NOTE: \*To the primary site

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics
* At least 4 weeks since prior radiotherapy to the primary tumor site and recovered
* No prior radiotherapy to more than 25% of the functional bone marrow

Surgery

* See Disease Characteristics
* Prior surgical resection allowed

Other

* No concurrent participation in supportive care trials
* Concurrent enrollment on protocol ECOG-E1Y03 allowed

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Comprehensive Cancer Institute
state: Alabama
city: Scottsdale
country: United States
facility: CCOP - Mayo Clinic Scottsdale Oncology Program
state: Arizona
city: Aurora
country: United States
facility: Medical Center of Aurora - South Campus
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Denver Rose
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Incorporated
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Hope Cancer Care Center at Longmont United Hospital
state: Colorado
city: Pueblo
country: United States
facility: St. Mary-Corwin Regional Medical Center
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Cancer Centers - Thornton
state: Colorado
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Decatur
country: United States
facility: Veterans Affairs Medical Center - Atlanta (Decatur)
state: Georgia
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: La Grange
country: United States
facility: La Grange Oncology Associates
state: Illinois
city: Rockford
country: United States
facility: Swedish-American Regional Cancer Center
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Veterans Affairs Medical Center - Wichita
state: Kansas
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Cancer Center at Tufts - New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: MBCCOP - University of New Mexico HSC
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Cleveland
country: United States
facility: MetroHealth's Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Tulsa
country: United States
facility: CCOP - Oklahoma
state: Oklahoma
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center at the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hillman Cancer Center at University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
state: Tennessee
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
city: Pretoria
country: South Africa
facility: Pretoria Academic Hospital
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Elizabeth A. Poplin, MD
role: STUDY_CHAIR
References:
citation: Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, Alberts S, O'Dwyer P, Haller D, Catalano P, Cella D, Benson AB 3rd. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009 Aug 10;27(23):3778-85. doi: 10.1200/JCO.2008.20.9007. Epub 2009 Jul 6.
citation: Liebes L, Levy DE, Poplin E, et al.: Gemcitabine (G) plasma and intracellular pharmacokinetics in E6201: greater metabolite levels using fixed dosing rate (FDR) delivery. [Abstract] J Clin Oncol 24 (Suppl 18): A-2024, 2006.
citation: Poplin E, Levy DE, Berlin J, et al.: Phase III trial of gemcitabine (30-minute infusion) versus gemcitabine (fixed-dose-rate infusion[FDR]) versus gemcitabine + oxaliplatin(GEMOX) in patients with advanced pancreatic cancer (E6201). [Abstract] J Clin Oncol 24 (Suppl 18): A-LBA4004, 180s, 2006.