Clinical trial NCT00023972: Gemcitabine With or Without Exatecan Mesylate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Official title: A Randomized, Open-Label, Multicenter Phase III Study Comparing the Efficacy and Safety of a Combination of Intravenous DX-8951f (Exatecan Mesylate) Plus Gemcitabine to Gemcitabine Alone in Patients With Locally Advanced or Metastatic Cancer of the Exocrine Pancreas Who Have Not Received Prior Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: stage III pancreatic cancer
stage IV pancreatic cancer
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2003-01-27
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 use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if gemcitabine is more effective with or without exatecan mesylate in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of gemcitabine alone to that of gemcitabine and exatecan mesylate in treating patients who have locally advanced or metastatic pancreatic cancer.

Detailed description: OBJECTIVES:

* Compare the overall survival of patients with chemotherapy-naive locally advanced or metastatic cancer of the exocrine pancreas treated with exatecan mesylate and gemcitabine versus gemcitabine alone.
* Compare the measures of clinical benefit in patients treated with these regimens.
* Compare the anti-tumor efficacy of these regimens in this patient population.
* Determine the safety profile of exatecan mesylate and gemcitabine in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to performance status (60% vs 70-80% vs 90-100%), extent of disease (locally advanced vs metastatic), and prior radiotherapy for pancreatic cancer (yes or no). Patients are randomized to one of two treatment arms.

* Arm I: Patients receive exatecan mesylate (DX-8951f) IV over 30 minutes immediately followed by gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive gemcitabine IV over 30 minutes once weekly for up to 7 weeks followed by one week of rest (course 1). For all subsequent courses, patients receive gemcitabine once weekly for 3 weeks followed by one week of rest. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly.

PROJECTED ACCRUAL: Approximately 340 patients (170 per treatment arm) will be accrued for this study within 18 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed epithelial cancer of the exocrine pancreas

  * Locally advanced (unresectable) or metastatic disease
* No islet cell tumor, lymphoma, or sarcoma of the pancreas
* No known brain metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm3
* Platelet count at least 100,000/mm3

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* AST no greater than 5 times ULN
* Albumin at least 2.8 g/dL

Renal:

* Creatinine no greater than 1.5 times ULN

Cardiovascular:

* No active congestive heart failure
* No uncontrolled angina
* No myocardial infarction

Other:

* No serious infection or life-threatening illness unrelated to tumor
* No other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
* No overt psychosis or incompetency that would preclude study
* No history of a positive serology for HIV
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior systemic anticancer immunotherapy for pancreatic cancer
* No concurrent anticancer immunotherapy or other biologic therapy

Chemotherapy:

* No prior systemic anticancer chemotherapy for pancreatic cancer
* Prior fluorouracil as a radiosensitizer allowed
* No prior gemcitabine as a radiosensitizer
* No other concurrent anticancer chemotherapy

Endocrine therapy:

* Concurrent megestrol for appetite stimulation allowed

Radiotherapy:

* At least 28 days since prior radiotherapy and recovered
* No prior radiotherapy to more than 25% of estimated bone marrow reserve
* No concurrent anticancer radiotherapy

Surgery:

* At least 28 days since prior major surgery and recovered
* No concurrent surgery for cancer

Other:

* No prior investigational or other systemic anticancer therapy for pancreatic cancer
* No other concurrent investigational drugs

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Intouch Research
state: Alabama
city: Mobile
country: United States
facility: Providence Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Gilroy
country: United States
facility: Medical Oncology/Hematology
state: California
city: Greenbrae
country: United States
facility: California Cancer Care, Inc.
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Rancho Mirage
country: United States
facility: Cancer and Blood Institute of the Desert
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Hamden
country: United States
facility: Medical Oncology and Hematology, P.C.
state: Connecticut
city: Melbourne
country: United States
facility: nTouch Research
state: Florida
city: Miami
country: United States
facility: Sylvester Cancer Center, University of Miami
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center Orlando
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology and Oncology Consultants, P.C.
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Macon
country: United States
facility: Central Georgia Hematology Oncology, P.C.
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Park Ridge
country: United States
facility: Lutheran General Cancer Care Center
state: Illinois
city: Terre Haute
country: United States
facility: Hope Center
state: Indiana
city: Baltimore
country: United States
facility: Harbor Hospital Center
state: Maryland
city: Clinton
country: United States
facility: Oncology-Hematology Associates, P.A.
state: Maryland
city: Southfield
country: United States
facility: Providence Hospital Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Saint Joseph
country: United States
facility: St. Joseph Oncology, Inc.
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University Health Sciences Center
state: Missouri
city: Saint Louis
country: United States
facility: Midwest Hematology Oncology Consultants, Ltd.
state: Missouri
city: Billings
country: United States
facility: Billings Oncology Associates
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Las Vegas
country: United States
facility: Nevada Cancer Center
state: Nevada
city: Cherry Hill
country: United States
facility: Center for Cancer And Hematologic Disease
state: New Jersey
city: Morristown
country: United States
facility: Hematology Oncology Associates
state: New Jersey
city: Somerset
country: United States
facility: Hematology and Oncology Group
state: New Jersey
city: Summit
country: United States
facility: Summit Medical Group, P.A.
state: New Jersey
city: Brooklyn
country: United States
facility: HemOnCare, P.C.
state: New York
city: Cooperstown
country: United States
facility: Mary Imogene Bassett Hospital
state: New York
city: Lake Success
country: United States
facility: Nassau Hematology/Oncology PC
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: State University of New York Health Sciences Center - Stony Brook
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Williamsville
country: United States
facility: Buffalo Medical Group, P.C.
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Hickory
country: United States
facility: N.W. Carolina Oncology & Hematology, P.A.
state: North Carolina
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Mid-Ohio Oncology/Hematology, Inc.
state: Ohio
city: Kingston
country: United States
facility: Medical Oncology Associates of Wyoming Valley, P.C.
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Chattanooga
country: United States
facility: Memorial Hospital Cancer Center - Chattanooga
state: Tennessee
city: Franklin
country: United States
facility: Williamson Medical Center
state: Tennessee
city: Germantown
country: United States
facility: Family Cancer Center
state: Tennessee
city: Jackson
country: United States
facility: Jackson-Madison County General Hospital
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon-Minnie Pearl Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Provo
country: United States
facility: Central Utah Medical Clinic
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Hematology/Oncology Associates, Inc.
state: Utah
city: Puyallup
country: United States
facility: Rainier Oncology
state: Washington
city: Yakima
country: United States
facility: Yakima Regional Cancer Care Center
state: Washington
city: Wausau
country: United States
facility: UW Cancer Center Wausau Hospital
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Sudbury
country: Canada
facility: Northeastern Ontario Regional Cancer Centre, Sudbury
state: Ontario
city: Windsor
country: Canada
facility: Cancer Care Ontario - Windsor Regional Cancer Centre
state: Ontario
city: Charlottetown
country: Canada
facility: Queen Elizabeth Hospital, PEI
state: Prince Edward Island
city: Montreal
country: Canada
facility: CHUM Hopital Saint-Luc
state: Quebec
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: San Juan
country: Puerto Rico
facility: Veterans Affairs Medical Center - San Juan
Study officials:
affiliation: Daiichi Sankyo
name: Robert L. DeJager, MD, FACP
role: STUDY_CHAIR
References:
citation: Abou-Alfa GK, Letourneau R, Harker G, Modiano M, Hurwitz H, Tchekmedyian NS, Feit K, Ackerman J, De Jager RL, Eckhardt SG, O'Reilly EM. Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol. 2006 Sep 20;24(27):4441-7. doi: 10.1200/JCO.2006.07.0201.