Clinical trial NCT00026338: Gemcitabine With/Out Erlotinib in Unresectable Locally Advanced/Metastatic Pancreatic Cancer
Official title: A Randomized Placebo Controlled Study Of OSI-774 (TARCEVA) Plus Gemcitabine In Patients With Locally Advanced, Unresectable Or Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: stage III pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 569
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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. 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: 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.

Eligibility 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

Primary outcomes:
measure: Overall survival
timeFrame: 3 years
Secondary outcomes:
measure: Progression free survival
timeFrame: 3 years
measure: Quality of Life
timeFrame: 3 years
measure: Response rates
timeFrame: 3 years
measure: Toxicity
timeFrame: 3 years
measure: EGFR levels
timeFrame: 3 years
measure: Pharmacokinetics
timeFrame: 3 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Berkeley
country: United States
facility: Alta Bates Comprehensive Cancer Center
state: California
city: Greenbrae
country: United States
facility: Sutter Health West Cancer Research Group
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Institute
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Los Angeles
country: United States
facility: Kenmar Research Institute
state: California
city: Los Angeles
country: United States
facility: Century City Hospital
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
state: California
city: Manchester
country: United States
facility: Davis, Posteraro, & Wasser, MDs, LLP
state: Connecticut
city: New Britain
country: United States
facility: New Britain General Hospital
state: Connecticut
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Stamford
country: United States
facility: Hematology Oncology, P.C.
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Miami
country: United States
facility: Oncology-Hematology Group of South Florida
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Tamarac
country: United States
facility: Oncology & Hematology Associates of West Broward
state: Florida
city: Tampa
country: United States
facility: Moffitt Clinic at Tampa General Hospital
state: Florida
city: Macon
country: United States
facility: Central Georgia Hematology Oncology, P.C.
state: Georgia
city: Boise
country: United States
facility: Mountain States Tumor Institute
state: Idaho
city: Arlington Heights
country: United States
facility: Northwest Medical Specialists, P.C.
state: Illinois
city: Hines
country: United States
facility: Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)
state: Illinois
city: Peoria
country: United States
facility: Oncology/Hematology Associates of Central Illinois, P.C.
state: Illinois
city: Skokie
country: United States
facility: Midwest Cancer Research Group, Inc.
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Muncie
country: United States
facility: Medical Consultants
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Lucille Parker Markey Cancer Center, University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Norton Healthcare Pavilion
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: Annapolis
country: United States
facility: Annapolis Medical Specialists
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Tuft-New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: St. Elizabeth's Medical Center
state: Massachusetts
city: Pittsfield
country: United States
facility: Berkshire Physicians and Surgeons, P.C.
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: Midwest Oncology Consortium
state: Missouri
city: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology PA
state: New Hampshire
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: Mount Holly
country: United States
facility: Hematology-Oncology Associates
state: New Jersey
city: Voorhees
country: United States
facility: Cooper Cancer Institute
state: New Jersey
city: Glens Falls
country: United States
facility: Cancer Center at Glens Falls Hospital
state: New York
city: Great Neck
country: United States
facility: Arena Oncology Associates
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: Rochester
country: United States
facility: Interlakes Oncology/Hematology PC
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital
state: New York
city: Stony Brook
country: United States
facility: University Hospital - Stony Brook
state: New York
city: Charlotte
country: United States
facility: Presbyterian Hospital
state: North Carolina
city: Bismarck
country: United States
facility: Mid Dakota Clinic, P.C.
state: North Dakota
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Portland
country: United States
facility: Earle A. Chiles Research Institute at Providence Portland Medical Center
state: Oregon
city: Dunmore
country: United States
facility: Hematology-Oncology Association of NE Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology-Oncology, P.A.
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon-Minnie Pearl Cancer Center
state: Tennessee
city: Arlington
country: United States
facility: Arlington Cancer Center
state: Texas
city: Austin
country: United States
facility: Southwest Regional Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Cancer Care
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: Tyler Hematology Oncology, P.A.
state: Texas
city: Bennington
country: United States
facility: Green Mountain Oncology Group
state: Vermont
city: Mechanicsville
country: United States
facility: Hematology & Oncology Associates of Virginia
state: Virginia
city: Olympia
country: United States
facility: Western Washington Oncology
state: Washington
city: Vancouver
country: United States
facility: Southwest Washington Medical Center
state: Washington
city: Glendale
country: United States
facility: Oncology of Wisconsin
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital Britanico
city: Buenos Aires
country: Argentina
facility: Instituto de Oncologia Angel H. Roffo
city: Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming
city: Buenos Aires
country: Argentina
facility: Hospital Churruca
city: Buenos Aires
country: Argentina
facility: Hospital Italiano
city: Lanus
country: Argentina
facility: Hospital Interzonal De Augudos Euita
city: San Isidro
country: Argentina
facility: Confidence Medical Center
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Newcastle Mater Misericordiae Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Institute of Oncology
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Ashford
country: Australia
facility: Ashford Cancer Centre
state: South Australia
city: Woodville
country: Australia
facility: Queen Elizabeth Hospital
state: South Australia
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin and Repatriation Medical Centre
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Institute
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Bahia
country: Brazil
facility: Nucleo de Oncologia da Bahia
city: Porto Alegre
country: Brazil
facility: Hospital Santa Rita Irtmandade Santa Casa De Porto Alegre
city: Sao Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency - Centre for the Southern Interior
state: British Columbia
city: Penticton
country: Canada
facility: Penticton Regional Hospital
state: British Columbia
city: Surrey
country: Canada
facility: British Columbia Cancer Agency - Fraser Valley Cancer Centre
state: British Columbia
city: Victoria
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: St. Johns
country: Canada
facility: Newfoundland Cancer Treatment and Research Foundation
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science Centre
state: Nova Scotia
city: Barrie
country: Canada
facility: Royal Victoria Hospital, Barrie
state: Ontario
city: Hamilton
country: Canada
facility: Cancer Care Ontario-Hamilton Regional Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Hospital
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Peterborough
country: Canada
facility: Peterborough Oncology Clinic
state: Ontario
city: Sault Sainte Marie
country: Canada
facility: Algoma District Medical Group
state: Ontario
city: St. Catharines
country: Canada
facility: Hotel Dieu Health Sciences Hospital - Niagara
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Ontario Cancer Institute
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Saint Joseph's Health Centre - Toronto
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Du Sacre-Coeur de Montreal
state: Quebec
city: Ste-Foy
country: Canada
facility: L'Hopital Laval
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Santiago
country: Chile
facility: Clinica Las Condes
city: Hong Kong
country: China
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: China
facility: Queen Mary Hospital
city: Berlin
country: Germany
facility: Virchow Klinikum Humboldt Universitaet Berlin
city: Essen
country: Germany
facility: Universitaetsklinik und Strahlenklinik - Essen
city: Frankfurt
country: Germany
facility: Stadtische Kliniken Frankfurt-Hochst
city: Freiburg
country: Germany
facility: Tumor Biology Center at the Albert - Ludwigs University
city: Halle
country: Germany
facility: Martin Luther Universitaet
city: Heidelberg
country: Germany
facility: Medizinische Universitaetsklinik und Poliklinik
city: Homburg/Saar
country: Germany
facility: Universitatsklinik, Saarland
city: Wurzburg
country: Germany
facility: University Wurzburg
city: Iraklion (Heraklion)
country: Greece
facility: University Hospital of Heraklion
state: Crete
city: Thessaloniki
country: Greece
facility: Theagenio Medical Institute
city: Thessaloniki
country: Greece
facility: Hippokration Hospital
city: Shatin, New Territories
country: Hong Kong
facility: Prince of Wales Hospital
city: Afula
country: Israel
facility: Haemek Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Campus
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center - Golda-Hasharon Campus
city: Rehovot
country: Israel
facility: Kaplan Hospital
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Palermo
country: Italy
facility: Policlinico - Cattedra di Ematologia
city: Tlalpan
country: Mexico
facility: Instituto Nac de Cancerologia
state: Distrito Federal
city: Dviango
country: Mexico
facility: Centro Estatal de Cancerologia
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Poznan
country: Poland
facility: Great Poland Cancer Center
city: Wroclaw
country: Poland
facility: Dolnoslaskie Centrum Oncology
city: Bucarest
country: Romania
facility: Institute of Oncology - Bucarest
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic-Universitatea de Medicina
city: Lasi
country: Romania
facility: St. Spiridon University Hospital
city: Sibiu
country: Romania
facility: Clinical County Hospital of Sibiu
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre - Singapore
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Edmonton, London
country: United Kingdom
facility: North Middlesex Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Center
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Guy's and St. Thomas' Hospitals NHS Trust
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital N.H.S. Trust
state: England
city: Newcastle upon Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment
state: England
city: Southampton
country: United Kingdom
facility: Royal South Hants Hospital
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: Belfast
country: United Kingdom
facility: Belfast City Hospital Trust
state: Northern Ireland
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
state: Wales
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Malcolm J. Moore, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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. 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. 2023 Oct 20;41(30):4714-4720. doi: 10.1200/JCO.22.02770.