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

NCT ID: NCT00026338

Last Updated: 2020-04-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

569 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-10-29

Study Completion Date

2009-02-10

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pancreatic Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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OSI-774 plus Gemcitabine

Group Type ACTIVE_COMPARATOR

erlotinib hydrochloride

Intervention Type DRUG

150 mg po daily

gemcitabine hydrochloride

Intervention Type DRUG

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)

Placebo plus gemcitabine

Group Type ACTIVE_COMPARATOR

gemcitabine hydrochloride

Intervention Type DRUG

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)

Interventions

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erlotinib hydrochloride

150 mg po daily

Intervention Type DRUG

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)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NCIC Clinical Trials Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Malcolm J. Moore, MD

Role: STUDY_CHAIR

Princess Margaret Hospital, Canada

Locations

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Arizona Clinical Research Center

Tucson, Arizona, United States

Site Status

Highlands Oncology Group

Springdale, Arkansas, United States

Site Status

Alta Bates Comprehensive Cancer Center

Berkeley, California, United States

Site Status

Sutter Health West Cancer Research Group

Greenbrae, California, United States

Site Status

Loma Linda University Cancer Institute

Loma Linda, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

Kenmar Research Institute

Los Angeles, California, United States

Site Status

Century City Hospital

Los Angeles, California, United States

Site Status

David Geffen School of Medicine

Los Angeles, California, United States

Site Status

Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego

San Diego, California, United States

Site Status

Davis, Posteraro, & Wasser, MDs, LLP

Manchester, Connecticut, United States

Site Status

New Britain General Hospital

New Britain, Connecticut, United States

Site Status

Eastern Connecticut Hematology and Oncology Associates

Norwich, Connecticut, United States

Site Status

Hematology Oncology, P.C.

Stamford, Connecticut, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

Oncology-Hematology Group of South Florida

Miami, Florida, United States

Site Status

Ocala Oncology Center

Ocala, Florida, United States

Site Status

Oncology & Hematology Associates of West Broward

Tamarac, Florida, United States

Site Status

Moffitt Clinic at Tampa General Hospital

Tampa, Florida, United States

Site Status

Central Georgia Hematology Oncology, P.C.

Macon, Georgia, United States

Site Status

Mountain States Tumor Institute

Boise, Idaho, United States

Site Status

Northwest Medical Specialists, P.C.

Arlington Heights, Illinois, United States

Site Status

Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)

Hines, Illinois, United States

Site Status

Oncology/Hematology Associates of Central Illinois, P.C.

Peoria, Illinois, United States

Site Status

Midwest Cancer Research Group, Inc.

Skokie, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

Medical Consultants

Muncie, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Lucille Parker Markey Cancer Center, University of Kentucky

Lexington, Kentucky, United States

Site Status

Norton Healthcare Pavilion

Louisville, Kentucky, United States

Site Status

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Site Status

Metairie, Louisiana, United States

Site Status

Tulane Cancer Center

New Orleans, Louisiana, United States

Site Status

Annapolis Medical Specialists

Annapolis, Maryland, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Tuft-New England Medical Center

Boston, Massachusetts, United States

Site Status

St. Elizabeth's Medical Center

Boston, Massachusetts, United States

Site Status

Berkshire Physicians and Surgeons, P.C.

Pittsfield, Massachusetts, United States

Site Status

Baystate Medical Center

Springfield, Massachusetts, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Midwest Oncology Consortium

Kansas City, Missouri, United States

Site Status

New Hampshire Oncology-Hematology PA

Hooksett, New Hampshire, United States

Site Status

St. Barnabas Medical Center

Livingston, New Jersey, United States

Site Status

Hematology-Oncology Associates

Mount Holly, New Jersey, United States

Site Status

Cooper Cancer Institute

Voorhees Township, New Jersey, United States

Site Status

Cancer Center at Glens Falls Hospital

Glens Falls, New York, United States

Site Status

Arena Oncology Associates

Great Neck, New York, United States

Site Status

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Site Status

Beth Israel Medical Center

New York, New York, United States

Site Status

Interlakes Oncology/Hematology PC

Rochester, New York, United States

Site Status

Staten Island University Hospital

Staten Island, New York, United States

Site Status

University Hospital - Stony Brook

Stony Brook, New York, United States

Site Status

Presbyterian Hospital

Charlotte, North Carolina, United States

Site Status

Mid Dakota Clinic, P.C.

Bismarck, North Dakota, United States

Site Status

University Hospitals of Cleveland

Cleveland, Ohio, United States

Site Status

Earle A. Chiles Research Institute at Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Hematology-Oncology Association of NE Pennsylvania

Dunmore, Pennsylvania, United States

Site Status

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Charleston Hematology-Oncology, P.A.

Charleston, South Carolina, United States

Site Status

Sarah Cannon-Minnie Pearl Cancer Center

Nashville, Tennessee, United States

Site Status

Arlington Cancer Center

Arlington, Texas, United States

Site Status

Southwest Regional Cancer Center

Austin, Texas, United States

Site Status

Texas Cancer Care

Fort Worth, Texas, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Tyler Hematology Oncology, P.A.

Tyler, Texas, United States

Site Status

Green Mountain Oncology Group

Bennington, Vermont, United States

Site Status

Hematology & Oncology Associates of Virginia

Mechanicsville, Virginia, United States

Site Status

Western Washington Oncology

Olympia, Washington, United States

Site Status

Southwest Washington Medical Center

Vancouver, Washington, United States

Site Status

Oncology of Wisconsin

Glendale, Wisconsin, United States

Site Status

Hospital Britanico

Buenos Aires, , Argentina

Site Status

Instituto de Oncologia Angel H. Roffo

Buenos Aires, , Argentina

Site Status

Instituto Alexander Fleming

Buenos Aires, , Argentina

Site Status

Hospital Churruca

Buenos Aires, , Argentina

Site Status

Hospital Italiano

Buenos Aires, , Argentina

Site Status

Hospital Interzonal De Augudos Euita

Lanús, , Argentina

Site Status

Confidence Medical Center

San Isidro, , Argentina

Site Status

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

Newcastle Mater Misericordiae Hospital

Newcastle, New South Wales, Australia

Site Status

Institute of Oncology

Randwick, New South Wales, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Ashford Cancer Centre

Ashford, South Australia, Australia

Site Status

Queen Elizabeth Hospital

Woodville, South Australia, Australia

Site Status

Frankston Hospital

Frankston, Victoria, Australia

Site Status

Austin and Repatriation Medical Centre

Heidelberg, Victoria, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

Peter MacCallum Cancer Institute

Melbourne, , Australia

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

Nucleo de Oncologia da Bahia

Bahia, , Brazil

Site Status

Hospital Santa Rita Irtmandade Santa Casa De Porto Alegre

Porto Alegre, , Brazil

Site Status

Hospital Israelita Albert Einstein

São Paulo, , Brazil

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, Canada

Site Status

Penticton Regional Hospital

Penticton, British Columbia, Canada

Site Status

British Columbia Cancer Agency - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

Site Status

British Columbia Cancer Agency

Victoria, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Site Status

Newfoundland Cancer Treatment and Research Foundation

St. John's, Newfoundland and Labrador, Canada

Site Status

Queen Elizabeth II Health Science Centre

Halifax, Nova Scotia, Canada

Site Status

Royal Victoria Hospital, Barrie

Barrie, Ontario, Canada

Site Status

Cancer Care Ontario-Hamilton Regional Cancer Centre

Hamilton, Ontario, Canada

Site Status

Kingston Regional Cancer Centre

Kingston, Ontario, Canada

Site Status

Cancer Care Ontario-London Regional Cancer Centre

London, Ontario, Canada

Site Status

Credit Valley Hospital

Mississauga, Ontario, Canada

Site Status

Southlake Regional Health Centre

Newmarket, Ontario, Canada

Site Status

Ottawa Regional Cancer Centre

Ottawa, Ontario, Canada

Site Status

Peterborough Oncology Clinic

Peterborough, Ontario, Canada

Site Status

Algoma District Medical Group

Sault Ste. Marie, Ontario, Canada

Site Status

Hotel Dieu Health Sciences Hospital - Niagara

St. Catharines, Ontario, Canada

Site Status

Toronto East General Hospital

Toronto, Ontario, Canada

Site Status

Toronto Sunnybrook Regional Cancer Centre

Toronto, Ontario, Canada

Site Status

Ontario Cancer Institute

Toronto, Ontario, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Saint Joseph's Health Centre - Toronto

Toronto, Ontario, Canada

Site Status

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Site Status

Hopital Du Sacre-Coeur de Montreal

Montreal, Quebec, Canada

Site Status

L'Hopital Laval

Ste-Foy, Quebec, Canada

Site Status

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Site Status

Clinica Las Condes

Santiago, , Chile

Site Status

Pamela Youde Nethersole Eastern Hospital

Hong Kong, , China

Site Status

Queen Mary Hospital

Hong Kong, , China

Site Status

Virchow Klinikum Humboldt Universitaet Berlin

Berlin, , Germany

Site Status

Universitaetsklinik und Strahlenklinik - Essen

Essen, , Germany

Site Status

Stadtische Kliniken Frankfurt-Hochst

Frankfurt, , Germany

Site Status

Tumor Biology Center at the Albert - Ludwigs University

Freiburg im Breisgau, , Germany

Site Status

Martin Luther Universitaet

Halle, , Germany

Site Status

Medizinische Universitaetsklinik und Poliklinik

Heidelberg, , Germany

Site Status

Universitatsklinik, Saarland

Homburg/Saar, , Germany

Site Status

University Wurzburg

Würzburg, , Germany

Site Status

University Hospital of Heraklion

Iraklion (Heraklion), Crete, Greece

Site Status

Theagenio Medical Institute

Thessaloniki, , Greece

Site Status

Hippokration Hospital

Thessaloniki, , Greece

Site Status

Prince of Wales Hospital

Shatin, New Territories, , Hong Kong

Site Status

Haemek Medical Center

Afula, , Israel

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Rabin Medical Center - Beilinson Campus

Petah Tikva, , Israel

Site Status

Rabin Medical Center - Golda-Hasharon Campus

Petah Tikva, , Israel

Site Status

Kaplan Hospital

Rehovot, , Israel

Site Status

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Sheba Medical Center

Tel Litwinsky, , Israel

Site Status

Policlinico - Cattedra di Ematologia

Palermo, , Italy

Site Status

Instituto Nac de Cancerologia

Tlalpan, Mexico City, Mexico

Site Status

Centro Estatal de Cancerologia

Dviango, , Mexico

Site Status

Auckland Hospital

Auckland, , New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Great Poland Cancer Center

Poznan, , Poland

Site Status

Dolnoslaskie Centrum Oncology

Wroclaw, , Poland

Site Status

Institute of Oncology - Bucarest

Bucharest, , Romania

Site Status

Institutul Oncologic-Universitatea de Medicina

Cluj-Napoca, , Romania

Site Status

St. Spiridon University Hospital

Lasi, , Romania

Site Status

Clinical County Hospital of Sibiu

Sibiu, , Romania

Site Status

National University Hospital

Singapore, , Singapore

Site Status

Singapore General Hospital

Singapore, , Singapore

Site Status

National Cancer Centre - Singapore

Singapore, , Singapore

Site Status

Queen Elizabeth Hospital

Birmingham, England, United Kingdom

Site Status

North Middlesex Hospital

Edmonton, London, England, United Kingdom

Site Status

St. Luke's Cancer Center

Guildford, England, United Kingdom

Site Status

Princess Royal Hospital

Hull, England, United Kingdom

Site Status

Saint Bartholomew's Hospital

London, England, United Kingdom

Site Status

Guy's and St. Thomas' Hospitals NHS Trust

London, England, United Kingdom

Site Status

Christie Hospital N.H.S. Trust

Manchester, England, United Kingdom

Site Status

Northern Centre for Cancer Treatment

Newcastle upon Tyne, England, United Kingdom

Site Status

Royal South Hants Hospital

Southampton, England, United Kingdom

Site Status

New Cross Hospital

Wolverhampton, England, United Kingdom

Site Status

Belfast City Hospital Trust

Belfast, Northern Ireland, United Kingdom

Site Status

Velindre Hospital

Cardiff, Wales, United Kingdom

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Countries

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

References

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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.

Reference Type BACKGROUND

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 Oncol 25 (Suppl 18): A-4521, 2007.

Reference Type RESULT

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 gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. doi: 10.1200/JCO.2006.07.9525. Epub 2007 Apr 23.

Reference Type RESULT
PMID: 17452677 (View on PubMed)

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 Society of Clinical Oncology 2005 Gastrointestinal Cancers Symposium, 27-29 January 2005, Miami, Florida. A-77, 2005.

Reference Type RESULT

Other Identifiers

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CAN-NCIC-PA3

Identifier Type: OTHER

Identifier Source: secondary_id

OSI-CAN-NCIC-PA3

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000069020

Identifier Type: OTHER

Identifier Source: secondary_id

PA3

Identifier Type: -

Identifier Source: org_study_id

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