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.

Condition	Treatment or Intervention	Phase
stage III pancreatic cancer adenocarcinoma of the pancreas stage IVA pancreatic cancer stage IVB pancreatic cancer	Drug: erlotinib  Drug: gemcitabine  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase III

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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/mm3
• Platelet count at least 100,000/mm3

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
• 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

Arizona
      Arizona Clinical Research Center, Tucson,  Arizona,  85712,  United States
Arkansas
      Highlands Oncology Group, Springdale,  Arkansas,  72764,  United States
California
      Alta Bates Comprehensive Cancer Center, Berkeley,  California,  94704,  United States
      Century City Hospital, Los Angeles,  California,  90067,  United States
      David Geffen School of Medicine, Los Angeles,  California,  90095-7059,  United States
      Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego, San Diego,  California,  92120,  United States
      Kenmar Research Institute, Los Angeles,  California,  90057,  United States
      Loma Linda University Cancer Institute, Loma Linda,  California,  92354,  United States
      Sutter Health West Cancer Research Group, Greenbrae,  California,  94904,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States
Connecticut
      Davis, Posteraro, & Wasser, MDs, LLP, Manchester,  Connecticut,  06040,  United States
      Eastern Connecticut Hematology and Oncology Associates, Norwich,  Connecticut,  06360,  United States
      Hematology Oncology, P.C., Stamford,  Connecticut,  06902,  United States
      New Britain General Hospital, New Britain,  Connecticut,  06050-2000,  United States
Florida
      Florida Cancer Specialists, Fort Myers,  Florida,  33901,  United States
      Moffitt Clinic at Tampa General Hospital, Tampa,  Florida,  33612-9497,  United States
      Ocala Oncology Center, Ocala,  Florida,  34471-5563,  United States
      Oncology & Hematology Associates of West Broward, Tamarac,  Florida,  33321,  United States
      Oncology-Hematology Group of South Florida, Miami,  Florida,  33176,  United States
Georgia
      Central Georgia Hematology Oncology, P.C., Macon,  Georgia,  31201,  United States
Idaho
      Mountain States Tumor Institute, Boise,  Idaho,  83712,  United States
Illinois
      Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      Midwest Cancer Research Group, Inc., Skokie,  Illinois,  60076,  United States
      Northwest Medical Specialists, P.C., Arlington Heights,  Illinois,  60004,  United States
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61602,  United States
      Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital), Hines,  Illinois,  60141,  United States
Indiana
      Medical Consultants, Muncie,  Indiana,  47304,  United States
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States
Kentucky
      Lucille Parker Markey Cancer Center, University of Kentucky, Lexington,  Kentucky,  40536-0093,  United States
      Norton Healthcare Pavilion, Louisville,  Kentucky,  40202,  United States
Louisiana
      Metairie,  Louisiana,  70006,  United States
      Mary Bird Perkins Cancer Center, Baton Rouge,  Louisiana,  70809,  United States
      Tulane Cancer Center, New Orleans,  Louisiana,  70112-2699,  United States
Maryland
      Annapolis Medical Specialists, Annapolis,  Maryland,  21401,  United States
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States
      Sinai Hospital of Baltimore, Baltimore,  Maryland,  21215,  United States
Massachusetts
      Baystate Medical Center, Springfield,  Massachusetts,  01199,  United States
      Berkshire Physicians and Surgeons, P.C., Pittsfield,  Massachusetts,  01201,  United States
      St. Elizabeth's Medical Center, Boston,  Massachusetts,  02135-2997,  United States
      Tuft-New England Medical Center, Boston,  Massachusetts,  02111,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
Missouri
      Midwest Oncology Consortium, Kansas City,  Missouri,  64111,  United States
New Hampshire
      New Hampshire Oncology-Hematology PA, Hooksett,  New Hampshire,  03106,  United States
New Jersey
      Cooper Cancer Institute, Voorhees,  New Jersey,  08043,  United States
      Hematology-Oncology Associates, Mount Holly,  New Jersey,  08060,  United States
      St. Barnabas Medical Center, Livingston,  New Jersey,  07039,  United States
New York
      Arena Oncology Associates, Great Neck,  New York,  11021,  United States
      Beth Israel Medical Center, New York,  New York,  10019,  United States
      Cancer Center at Glens Falls Hospital, Glens Falls,  New York,  12801,  United States
      Interlakes Oncology/Hematology PC, Rochester,  New York,  14623,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      Staten Island University Hospital, Staten Island,  New York,  10305,  United States
      University Hospital - Stony Brook, Stony Brook,  New York,  11794-8174,  United States
North Carolina
      Presbyterian Hospital, Charlotte,  North Carolina,  28233-3549,  United States
North Dakota
      Mid Dakota Clinic, P.C., Bismarck,  North Dakota,  58502-5538,  United States
Ohio
      University Hospitals of Cleveland, Cleveland,  Ohio,  44106,  United States
Oregon
      Earle A. Chiles Research Institute at Providence Portland Medical Center, Portland,  Oregon,  97213-2967,  United States
Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
      Hematology-Oncology Association of NE Pennsylvania, Dunmore,  Pennsylvania,  18512,  United States
      Pennsylvania Oncology Hematology Associates, Philadelphia,  Pennsylvania,  19106,  United States
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104,  United States
South Carolina
      Charleston Hematology-Oncology, P.A., Charleston,  South Carolina,  29403,  United States
Tennessee
      Sarah Cannon-Minnie Pearl Cancer Center, Nashville,  Tennessee,  37203,  United States
Texas
      Arlington Cancer Center, Arlington,  Texas,  76012,  United States
      Southwest Regional Cancer Center, Austin,  Texas,  78705,  United States
      Texas Cancer Care, Fort Worth,  Texas,  76104,  United States
      Tyler Hematology Oncology, P.A., Tyler,  Texas,  75701,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
Vermont
      Green Mountain Oncology Group, Bennington,  Vermont,  05201,  United States
Virginia
      Hematology & Oncology Associates of Virginia, Mechanicsville,  Virginia,  23116,  United States
Washington
      Southwest Washington Medical Center, Vancouver,  Washington,  98664,  United States
      Western Washington Oncology, Olympia,  Washington,  98502,  United States
Wisconsin
      Oncology of Wisconsin, Glendale,  Wisconsin,  53212,  United States
Argentina
      Confidence Medical Center, San Isidro,  1642,  Argentina
      Hospital Britanico, Buenos Aires,  1280,  Argentina
      Hospital Churruca, Buenos Aires,  1437,  Argentina
      Hospital Interzonal De Augudos Euita, Lanus,  1824,  Argentina
      Hospital Italiano, Buenos Aires,  CP1181ACH,  Argentina
      Instituto Alexander Fleming, Buenos Aires,  1426,  Argentina
      Instituto de Oncologia Angel H. Roffo, Buenos Aires,  1417,  Argentina
Australia
      Peter MacCallum Cancer Institute, Melbourne,  8006,  Australia
Australia, New South Wales
      Concord Repatriation General Hospital, Concord,  New South Wales,  2139,  Australia
      Institute of Oncology, Randwick,  New South Wales,  2031,  Australia
      Liverpool Hospital, Liverpool,  New South Wales,  2170,  Australia
      Newcastle Mater Misericordiae Hospital, Newcastle,  New South Wales,  NSW 2310,  Australia
Australia, South Australia
      Ashford Cancer Centre, Ashford,  South Australia,  5035,  Australia
      Queen Elizabeth Hospital, Woodville,  South Australia,  5011,  Australia
      Royal Adelaide Hospital, Adelaide,  South Australia,  5000,  Australia
Australia, Victoria
      Austin and Repatriation Medical Centre, Heidelberg,  Victoria,  3084,  Australia
      Frankston Hospital, Frankston,  Victoria,  3199,  Australia
Australia, Western Australia
      Royal Perth Hospital, Perth,  Western Australia,  6000,  Australia
Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
Brazil
      Hospital Israelita Albert Einstein, Sao Paulo,  05651-901,  Brazil
      Hospital Santa Rita Irtmandade Santa Casa De Porto Alegre, Porto Alegre,  91330-490,  Brazil
      Nucleo de Oncologia da Bahia, Bahia,  40170-070,  Brazil
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
Canada, British Columbia
      British Columbia Cancer Agency - Centre for the Southern Interior, Kelowna,  British Columbia,  V1Y 5L3,  Canada
      British Columbia Cancer Agency - Fraser Valley Cancer Centre, Surrey,  British Columbia,  V3V 1Z2,  Canada
      British Columbia Cancer Agency, Victoria,  British Columbia,  V8R 6V5,  Canada
      Penticton Regional Hospital, Penticton,  British Columbia,  V2A 3G6,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, New Brunswick
      Saint John Regional Hospital, Saint John,  New Brunswick,  E2L 4L2,  Canada
Canada, Newfoundland and Labrador
      Newfoundland Cancer Treatment and Research Foundation, St. Johns,  Newfoundland and Labrador,  A1B 3V6,  Canada
Canada, Nova Scotia
      Queen Elizabeth II Health Science Centre, Halifax,  Nova Scotia,  B3H 2Y9,  Canada
Canada, Ontario
      Algoma District Medical Group, Sault Sainte Marie,  Ontario,  P6B 1Y5,  Canada
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Credit Valley Hospital, Mississauga,  Ontario,  L5M 2N1,  Canada
      Hotel Dieu Health Sciences Hospital - Niagara, St. Catharines,  Ontario,  L2R 5K3,  Canada
      Kingston Regional Cancer Centre, Kingston,  Ontario,  K7L 5P9,  Canada
      Ontario Cancer Institute, Toronto,  Ontario,  M4X 1K9,  Canada
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 1C4,  Canada
      Peterborough Oncology Clinic, Peterborough,  Ontario,  K9H 7B6,  Canada
      Royal Victoria Hospital, Barrie, Barrie,  Ontario,  L4M 6M2,  Canada
      Saint Joseph's Health Centre - Toronto, Toronto,  Ontario,  M6R 1B5,  Canada
      Southlake Regional Health Centre, Newmarket,  Ontario,  L3Y 2P9,  Canada
      Toronto East General Hospital, Toronto,  Ontario,  M4C 3E7,  Canada
      Toronto General Hospital, Toronto,  Ontario,  M4X 1K9,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
Canada, Quebec
      Hopital Du Sacre-Coeur de Montreal, Montreal,  Quebec,  H4J 1C5,  Canada
      L'Hopital Laval, Ste Foy,  Quebec,  G1V 4G5,  Canada
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada
Canada, Saskatchewan
      Allan Blair Cancer Centre, Regina,  Saskatchewan,  S4T 7T1,  Canada
Chile
      Clinica Las Condes, Santiago,  Chile
China
      Pamela Youde Nethersole Eastern Hospital, Hong Kong,  China
      Queen Mary Hospital, Hong Kong,  China
Germany
      Martin Luther Universitaet, Halle,  DOH-06112,  Germany
      Medizinische Universitaetsklinik und Poliklinik, Heidelberg,  D-69115,  Germany
      Stadtische Kliniken Frankfurt-Hochst, Frankfurt,  DOH-65929,  Germany
      Tumor Biology Center at the Albert - Ludwigs University, Freiburg,  D-79106,  Germany
      Universitaetsklinik und Strahlenklinik - Essen, ESSEN,  D-45122,  Germany
      Universitatsklinik, Saarland, HOMBURG / SAAR,  D-66421,  Germany
      University Wurzburg, Wurzburg,  D-97070,  Germany
      Virchow Klinikum Humboldt Universitaet Berlin, Berlin,  D-13353,  Germany
Greece
      Hippokration Hospital, THESSALONIKI,  54642,  Greece
      Theagenio Medical Institute, THESSALONIKI,  540 07,  Greece
Greece, Crete
      University Hospital of Heraklion, Iraklion (Heraklion),  Crete,  71110,  Greece
Hong Kong
      Prince of Wales Hospital, Shatin, New Territories,  NT,  Hong Kong
Israel
      Haemek Medical Center, Afula,  18101,  Israel
      Kaplan Hospital, Rehovot,  76100,  Israel
      Rabin Medical Center - Beilinson Campus, Petah-Tikva,  49100,  Israel
      Rabin Medical Center - Golda-Hasharon Campus, Petah-Tikva,  49372,  Israel
      Rambam Medical Center, Haifa,  31096,  Israel
      Sheba Medical Center, Tel Hashomer,  52621,  Israel
      Tel-Aviv Sourasky Medical Center, Tel Aviv,  64239,  Israel
Italy
      Policlinico - Cattedra di Ematologia, Palermo,  90100,  Italy
Mexico
      Centro Estatal de Cancerologia, Dviango,  34000,  Mexico
Mexico, Distrito Federal
      Instituto Nac de Cancerologia, Tlalpan,  Distrito Federal,  22,  Mexico
New Zealand
      Auckland Hospital, Auckland,  1,  New Zealand
      Christchurch Hospital, Christchurch,  1,  New Zealand
Poland
      Dolnoslaskie Centrum Oncology, Wroclaw,  53-413,  Poland
      Great Poland Cancer Center, Poznan,  61 866,  Poland
Romania
      Clinical County Hospital of Sibiu, Sibiu,  2400,  Romania
      Institute of Oncology - Bucarest, Bucarest,  RO 72435,  Romania
      Institutul Oncologic-Universitatea de Medicina, Cluj Napoca,  3400,  Romania
      St. Spiridon University Hospital, Lasi,  6600,  Romania
Singapore
      National Cancer Centre - Singapore, Singapore,  169610,  Singapore
      National University Hospital, Singapore,  119074,  Singapore
      Singapore General Hospital, Singapore,  168609,  Singapore
United Kingdom
      Churchill Hospital, Oxford,  OX3 7LJ,  United Kingdom
United Kingdom, England
      Christie Hospital N.H.S. Trust, Manchester,  England,  M20 4BX,  United Kingdom
      Guy's and St. Thomas' Hospitals NHS Trust, London,  England,  SE1 9RT,  United Kingdom
      New Cross Hospital, Wolverhampton,  England,  WV10 0QP,  United Kingdom
      North Middlesex Hospital, Edmonton, London,  England,  NI8 1QX,  United Kingdom
      Northern Centre for Cancer Treatment, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom
      Princess Royal Hospital, Hull,  England,  HU8 9HE,  United Kingdom
      Queen Elizabeth Hospital, Birmingham,  England,  B18 7QH,  United Kingdom
      Royal South Hants Hospital, Southampton,  England,  SO14 0YG,  United Kingdom
      Saint Bartholomew's Hospital, London,  England,  EC1A 7BE,  United Kingdom
      St. Luke's Cancer Center, Guildford,  England,  GU2 5XX,  United Kingdom
United Kingdom, Northern Ireland
      Belfast City Hospital Trust, Belfast,  Northern Ireland,  BT9 7AB,  United Kingdom
United Kingdom, Wales
      Velindre Hospital, Cardiff,  Wales,  CF4 7XL,  United Kingdom

Study chairs or principal investigators

Malcolm J. Moore, MD,  Study Chair,  Ontario Cancer Institute   

Study ID Numbers:  CDR0000069020; CAN-NCIC-PA3; OSI-CAN-NCIC-PA3
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  November 9, 2001
ClinicalTrials.gov Identifier:  NCT00026338
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08