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

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. 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.

Official Title

A Randomized Placebo Controlled Study Of OSI-774 (TARCEVA) Plus Gemcitabine In Patients With Locally Advanced, Unresectable Or Metastatic Pancreatic Cancer

Conditions

Pancreatic Cancer

Study Type

Interventional

Study Design

Treatment

Further 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.

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.

1. 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.
2. 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.

Study Start

August 2001

Eligibility & Criteria

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

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:

1. Age: 18 and over
2. Performance status: ECOG 0-2
3. Life expectancy: Not specified
4. Hematopoietic: Absolute granulocyte count at least 1,500/mm³; Platelet count at least 100,000/mm³
5. 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)
6. Renal: Creatinine less than 1.5 times ULN
7. 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
8. 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
9. 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)
10. 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:

1. Biologic therapy: No concurrent biologic therapy or immunotherapy
2. 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
3. Endocrine therapy: Not specified
4. 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
5. Surgery: See Disease Characteristics; At least 2 weeks since prior major surgery; No concurrent ophthalmic surgery
6. 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

Total Enrolment

800

Contact Details

• Peter MacCallum Cancer Institute, Melbourne, 8006, 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

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

Victoria

• Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia
• Frankston Hospital, Frankston, Victoria, 3199, Australia

Western Australia

• Royal Perth Hospital, Perth, Western Australia, 6000, Australia