Gemcitabine With or Without Erlotinib in Treating Patients With Unresectable Locally Advanced or Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00026338
First received: November 9, 2001
Last updated: September 28, 2011
Last verified: September 2011
  Purpose

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 Intervention Phase
Pancreatic Cancer
Drug: erlotinib hydrochloride
Drug: gemcitabine hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Canada, US and selected countries only

  • Response rates [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Complete and partial response only.

  • Toxicity [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • EGFR levels [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Correlate the expression oftissue EGFR levels (at diagnosis) with outcomes and response to treatment

  • Pharmacokinetics [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To measure trough levels of081-774 (Tarceva™) to determine population pharmacokinetics


Enrollment: 569
Study Start Date: August 2001
Study Completion Date: February 2009
Primary Completion Date: September 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00026338

  Show 173 Study Locations
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Malcolm J. Moore, MD Princess Margaret Hospital, Canada
  More Information

Additional Information:
Publications:
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.
Moore MJ, Goldstein D, Hamm J, et al.: Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. [Abstract] J Clin Oncol 23 (Suppl 16): A-1, 1s, 2005.
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.

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00026338     History of Changes
Other Study ID Numbers: PA3, CAN-NCIC-PA3, OSI-CAN-NCIC-PA3, CDR0000069020
Study First Received: November 9, 2001
Last Updated: September 28, 2011
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by NCIC Clinical Trials Group:
stage III pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Erlotinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014