Gemcitabine With/Out Erlotinib in Unresectable Locally Advanced/Metastatic Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

A Randomized Placebo Controlled Study Of OSI-774 (TARCEVA) Plus Gemcitabine In Patients With Locally Advanced, Unresectable Or Metastatic Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00026338
• Other study ID #: PA3
• Secondary ID: CAN-NCIC-PA3OSI-
• Status: Completed
• Phase: Phase 3
• Start date: October 29, 2001
• Est. completion date: February 10, 2009

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies such as erlotinib use different ways to stimulate the immune system and stop cancer cells from growing. Combining chemotherapy and biological therapy may kill more tumor cells. It is not yet known if gemcitabine is more effective with or without erlotinib in treating pancreatic cancer.

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

Description:

OBJECTIVES:

• Compare the overall survival rate in patients with unresectable locally advanced or metastatic pancreatic cancer treated with gemcitabine with or without erlotinib.

• Compare the progression-free survival rate in patients treated with these regimens.

• Compare the quality of life of patients treated with these regimens.

• Compare the response rate and response duration in patients treated with these regimens.

• Compare the nature, severity, and frequency of toxic effects of these regimens in these patients.

• Correlate the expression of tissue epidermal growth factor receptor levels at diagnosis with outcome and response in patients treated with these regimens.

• Determine the pharmacokinetics of erlotinib in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center, extent of disease (locally advanced vs metastatic), and ECOG performance status (0-1 vs 2). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43 of course 1 only, which lasts 8 weeks, and on days 1, 8, and 15 of all subsequent courses, which last 4 weeks each. Patients also receive 1 of 2 doses of oral erlotinib once daily.

• Arm II: Patients receive gemcitabine as in arm I and 1 of 2 doses of oral placebo once daily.

Treatment continues in both arms in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, on day 29 of course 1, on day 1 of all subsequent courses, at 4 weeks after study, and then every 12 weeks until disease progression.

Patients are followed at 4 weeks and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A total of 800 patients (400 per treatment arm) will be accrued for this study within 11 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 569
• Est. completion date: February 10, 2009
• Est. primary completion date: September 17, 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

• Locally advanced or metastatic disease that is considered unresectable

• No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 2 times upper limit of normal (ULN)

• AST and/or ALT less than 2 times ULN (5 times ULN if liver metastases present)

Renal:

• Creatinine less than 1.5 times ULN

Cardiovascular:

• No uncontrolled high blood pressure

• No unstable angina

• No congestive heart failure

• No myocardial infarction within the past year

• No cardiac ventricular arrhythmias requiring medication

Gastrointestinal:

• No gastrointestinal (GI) tract disease resulting in an inability to take oral medication such as uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

• No post-surgical malabsorption characterized by:

• Uncontrolled diarrhea that results in weight loss and vitamin deficiency OR

• Requires IV hyperalimentation

• Pancreatic enzyme supplementation allowed provided that the above criteria are not met

Ophthalmic:

• No ocular inflammation or infection unless fully treated prior to study

• No significant ophthalmologic abnormalities, including the following:

• Severe dry eye syndrome

• Sjogren's syndrome

• Keratoconjunctivitis sicca

• Severe exposure keratopathy

• Disorders that would increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• HIV negative

• No serious active infection

• No other serious underlying medical, psychological, or geographical condition that would preclude study participation

• No prior allergic reaction to compounds with similar chemical or biologic composition to erlotinib

• No other prior malignancy within the past 5 years except cancer in situ or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biologic therapy or immunotherapy

Chemotherapy:

• No prior chemotherapy except fluorouracil (with or without leucovorin calcium) or gemcitabine administered concurrently with radiotherapy as a radiosensitizer

• No other concurrent cytotoxic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Chemotherapy

• At least 4 weeks since prior radiotherapy and recovered

• Prior radiotherapy for local disease allowed if evidence of disease progression has occurred

• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

• At least 2 weeks since prior major surgery

• No concurrent ophthalmic surgery

Other:

• No prior epidermal growth factor receptor inhibitors

• At least 2 weeks since prior investigational drug

• No other concurrent investigational drugs during and for at least 30 days after study

• No other concurrent anti-cancer therapy

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• erlotinib hydrochloride
150 mg po daily
• gemcitabine hydrochloride
1000 mg/m2 IV weekly (Cycle 1 -Day 1, 8, 15, 22, 29, 36, 43 of an 8 week cycle, Cycle 2 and subsequent cycles -Day 1,8 and 15 of a 4 week cycle)

Locations

Country	Name	City	State
Argentina	Hospital Britanico	Buenos Aires
Argentina	Hospital Churruca	Buenos Aires
Argentina	Hospital Italiano	Buenos Aires
Argentina	Instituto Alexander Fleming	Buenos Aires
Argentina	Instituto de Oncologia Angel H. Roffo	Buenos Aires
Argentina	Hospital Interzonal De Augudos Euita	Lanus
Argentina	Confidence Medical Center	San Isidro
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Ashford Cancer Centre	Ashford	South Australia
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Frankston Hospital	Frankston	Victoria
Australia	Austin and Repatriation Medical Centre	Heidelberg	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Peter MacCallum Cancer Institute	Melbourne
Australia	Newcastle Mater Misericordiae Hospital	Newcastle	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Institute of Oncology	Randwick	New South Wales
Australia	Queen Elizabeth Hospital	Woodville	South Australia
Belgium	Institut Jules Bordet	Brussels
Brazil	Nucleo de Oncologia da Bahia	Bahia
Brazil	Hospital Santa Rita Irtmandade Santa Casa De Porto Alegre	Porto Alegre
Brazil	Hospital Israelita Albert Einstein	Sao Paulo
Canada	Royal Victoria Hospital, Barrie	Barrie	Ontario
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Queen Elizabeth II Health Science Centre	Halifax	Nova Scotia
Canada	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario
Canada	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia
Canada	Kingston Regional Cancer Centre	Kingston	Ontario
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Credit Valley Hospital	Mississauga	Ontario
Canada	Hopital Du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Penticton Regional Hospital	Penticton	British Columbia
Canada	Peterborough Oncology Clinic	Peterborough	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Algoma District Medical Group	Sault Sainte Marie	Ontario
Canada	Hotel Dieu Health Sciences Hospital - Niagara	St. Catharines	Ontario
Canada	Newfoundland Cancer Treatment and Research Foundation	St. Johns	Newfoundland and Labrador
Canada	L'Hopital Laval	Ste-Foy	Quebec
Canada	British Columbia Cancer Agency - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Ontario Cancer Institute	Toronto	Ontario
Canada	Saint Joseph's Health Centre - Toronto	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency	Victoria	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Chile	Clinica Las Condes	Santiago
China	Pamela Youde Nethersole Eastern Hospital	Hong Kong
China	Queen Mary Hospital	Hong Kong
Germany	Virchow Klinikum Humboldt Universitaet Berlin	Berlin
Germany	Universitaetsklinik und Strahlenklinik - Essen	Essen
Germany	Stadtische Kliniken Frankfurt-Hochst	Frankfurt
Germany	Tumor Biology Center at the Albert - Ludwigs University	Freiburg
Germany	Martin Luther Universitaet	Halle
Germany	Medizinische Universitaetsklinik und Poliklinik	Heidelberg
Germany	Universitatsklinik, Saarland	Homburg/Saar
Germany	University Wurzburg	Wurzburg
Greece	University Hospital of Heraklion	Iraklion (Heraklion)	Crete
Greece	Hippokration Hospital	Thessaloniki
Greece	Theagenio Medical Institute	Thessaloniki
Hong Kong	Prince of Wales Hospital	Shatin, New Territories
Israel	Haemek Medical Center	Afula
Israel	Rambam Medical Center	Haifa
Israel	Rabin Medical Center - Beilinson Campus	Petah-Tikva
Israel	Rabin Medical Center - Golda-Hasharon Campus	Petah-Tikva
Israel	Kaplan Hospital	Rehovot
Israel	Sheba Medical Center	Tel Hashomer
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv
Italy	Policlinico - Cattedra di Ematologia	Palermo
Mexico	Centro Estatal de Cancerologia	Dviango
Mexico	Instituto Nac de Cancerologia	Tlalpan	Distrito Federal
New Zealand	Auckland Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
Poland	Great Poland Cancer Center	Poznan
Poland	Dolnoslaskie Centrum Oncology	Wroclaw
Romania	Institute of Oncology - Bucarest	Bucarest
Romania	Institutul Oncologic-Universitatea de Medicina	Cluj-Napoca
Romania	St. Spiridon University Hospital	Lasi
Romania	Clinical County Hospital of Sibiu	Sibiu
Singapore	National Cancer Centre - Singapore	Singapore
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
United Kingdom	Belfast City Hospital Trust	Belfast	Northern Ireland
United Kingdom	Queen Elizabeth Hospital	Birmingham	England
United Kingdom	Velindre Hospital	Cardiff	Wales
United Kingdom	North Middlesex Hospital	Edmonton, London	England
United Kingdom	St. Luke's Cancer Center	Guildford	England
United Kingdom	Princess Royal Hospital	Hull	England
United Kingdom	Guy's and St. Thomas' Hospitals NHS Trust	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	Christie Hospital N.H.S. Trust	Manchester	England
United Kingdom	Northern Centre for Cancer Treatment	Newcastle upon Tyne	England
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Royal South Hants Hospital	Southampton	England
United Kingdom	New Cross Hospital	Wolverhampton	England
United States	Annapolis Medical Specialists	Annapolis	Maryland
United States	Arlington Cancer Center	Arlington	Texas
United States	Northwest Medical Specialists, P.C.	Arlington Heights	Illinois
United States	Southwest Regional Cancer Center	Austin	Texas
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Mid Dakota Clinic, P.C.	Bismarck	North Dakota
United States	Mountain States Tumor Institute	Boise	Idaho
United States	St. Elizabeth's Medical Center	Boston	Massachusetts
United States	Tuft-New England Medical Center	Boston	Massachusetts
United States	Charleston Hematology-Oncology, P.A.	Charleston	South Carolina
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Hematology-Oncology Association of NE Pennsylvania	Dunmore	Pennsylvania
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Texas Cancer Care	Fort Worth	Texas
United States	Oncology of Wisconsin	Glendale	Wisconsin
United States	Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	Arena Oncology Associates	Great Neck	New York
United States	Sutter Health West Cancer Research Group	Greenbrae	California
United States	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois
United States	New Hampshire Oncology-Hematology PA	Hooksett	New Hampshire
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Midwest Oncology Consortium	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Lucille Parker Markey Cancer Center, University of Kentucky	Lexington	Kentucky
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	Loma Linda University Cancer Institute	Loma Linda	California
United States	Century City Hospital	Los Angeles	California
United States	David Geffen School of Medicine	Los Angeles	California
United States	Kenmar Research Institute	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Norton Healthcare Pavilion	Louisville	Kentucky
United States	Central Georgia Hematology Oncology, P.C.	Macon	Georgia
United States	Davis, Posteraro, & Wasser, MDs, LLP	Manchester	Connecticut
United States	Hematology & Oncology Associates of Virginia	Mechanicsville	Virginia
United States	Oncology-Hematology Group of South Florida	Miami	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Hematology-Oncology Associates	Mount Holly	New Jersey
United States	Medical Consultants	Muncie	Indiana
United States	Sarah Cannon-Minnie Pearl Cancer Center	Nashville	Tennessee
United States	New Britain General Hospital	New Britain	Connecticut
United States	Tulane Cancer Center	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Ocala Oncology Center	Ocala	Florida
United States	Western Washington Oncology	Olympia	Washington
United States	Oncology/Hematology Associates of Central Illinois, P.C.	Peoria	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Berkshire Physicians and Surgeons, P.C.	Pittsfield	Massachusetts
United States	Earle A. Chiles Research Institute at Providence Portland Medical Center	Portland	Oregon
United States	Interlakes Oncology/Hematology PC	Rochester	New York
United States	Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego	San Diego	California
United States	Midwest Cancer Research Group, Inc.	Skokie	Illinois
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Hematology Oncology, P.C.	Stamford	Connecticut
United States	Staten Island University Hospital	Staten Island	New York
United States	University Hospital - Stony Brook	Stony Brook	New York
United States	Oncology & Hematology Associates of West Broward	Tamarac	Florida
United States	Moffitt Clinic at Tampa General Hospital	Tampa	Florida
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	Tyler Hematology Oncology, P.A.	Tyler	Texas
United States	Carle Cancer Center	Urbana	Illinois
United States	Southwest Washington Medical Center	Vancouver	Washington
United States	Cooper Cancer Institute	Voorhees	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  Germany,  Greece,  Hong Kong,  Israel,  Italy,  Mexico,  New Zealand,  Poland,  Romania,  Singapore,  United Kingdom, 

References & Publications (4)

Dhani NC, Tu D, Parulekar W, et al.: A retrospective analysis of tumor size (TS) as a continuous rather than discrete variable in advanced pancreatic cancer. [Abstract] J Clin Oncol 27 (Suppl 15): A-e15565, 2009.

Moore MJ, da Cunha Santos G, Kamel-Reid S, et al.: The relationship of K-ras mutations and EGFR gene copy number to outcome in patients treated with Erlotinib on National Cancer Institute of Canada Clinical Trials Group trial study PA.3. [Abstract] J Clin

Moore MJ, Goldstein D, Hamm J, et al.: Erlotinib improves survival when added to gemcitabine in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. [Abstract] American So

Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus g — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		3 years
Secondary	Progression free survival		3 years
Secondary	Quality of Life	Canada, US and selected countries only	3 years
Secondary	Response rates	Complete and partial response only.	3 years
Secondary	Toxicity		3 years
Secondary	EGFR levels	Correlate the expression oftissue EGFR levels (at diagnosis) with outcomes and response to treatment	3 years
Secondary	Pharmacokinetics	To measure trough levels of081-774 (Tarceva™) to determine population pharmacokinetics	3 years