Los Angeles,
California
90057
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.
Study summary:
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.
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