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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00026338
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : April 2, 2020
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride Phase 3

Detailed Description:


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 569 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Placebo Controlled Study Of OSI-774 (TARCEVA) Plus Gemcitabine In Patients With Locally Advanced, Unresectable Or Metastatic Pancreatic Cancer
Actual Study Start Date : October 29, 2001
Actual Primary Completion Date : September 17, 2004
Actual Study Completion Date : February 10, 2009

Arm Intervention/treatment
Active Comparator: OSI-774 plus Gemcitabine Drug: erlotinib hydrochloride
150 mg po daily

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)

Active Comparator: Placebo plus gemcitabine 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)

Primary Outcome Measures :
  1. Overall survival [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 3 years ]
  2. Quality of Life [ Time Frame: 3 years ]
    Canada, US and selected countries only

  3. Response rates [ Time Frame: 3 years ]
    Complete and partial response only.

  4. Toxicity [ Time Frame: 3 years ]
  5. EGFR levels [ Time Frame: 3 years ]
    Correlate the expression oftissue EGFR levels (at diagnosis) with outcomes and response to treatment

  6. Pharmacokinetics [ Time Frame: 3 years ]
    To measure trough levels of081-774 (Tarceva™) to determine population pharmacokinetics

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed adenocarcinoma of the pancreas
  • Locally advanced or metastatic disease that is considered unresectable
  • No known CNS metastases



  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified


  • Absolute granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3


  • 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)


  • Creatinine less than 1.5 times ULN


  • 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


  • 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


  • 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)


  • 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


Biologic therapy:

  • No concurrent biologic therapy or immunotherapy


  • 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


  • 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


  • See Disease Characteristics
  • At least 2 weeks since prior major surgery
  • No concurrent ophthalmic surgery


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00026338

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Sponsors and Collaborators
NCIC Clinical Trials Group
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Study Chair: Malcolm J. Moore, MD Princess Margaret Hospital, Canada
Publications of Results:
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.
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.

Other Publications:
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.

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Responsible Party: NCIC Clinical Trials Group Identifier: NCT00026338    
Other Study ID Numbers: PA3
CAN-NCIC-PA3 ( Other Identifier: PDQ )
OSI-CAN-NCIC-PA3 ( Other Identifier: OSI )
CDR0000069020 ( Other Identifier: PDQ )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: April 2, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Canadian Cancer Trials Group ( NCIC Clinical Trials Group ):
stage III pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Erlotinib Hydrochloride
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors