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

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

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00026338
Enrollment
569
Registered
2003-01-27
Start date
2001-10-29
Completion date
2009-02-10
Last updated
2020-04-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pancreatic Cancer

Keywords

stage III pancreatic cancer, adenocarcinoma of the pancreas, stage IV pancreatic cancer

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.

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.

Interventions

DRUGerlotinib hydrochloride

150 mg po daily

DRUGgemcitabine 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)

Sponsors

NCIC Clinical Trials Group
Lead SponsorNETWORK

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion 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

Design outcomes

Primary

MeasureTime frame
Overall survival3 years

Secondary

MeasureTime frameDescription
Quality of Life3 yearsCanada, US and selected countries only
Response rates3 yearsComplete and partial response only.
Progression free survival3 years
EGFR levels3 yearsCorrelate the expression oftissue EGFR levels (at diagnosis) with outcomes and response to treatment
Pharmacokinetics3 yearsTo measure trough levels of081-774 (Tarceva™) to determine population pharmacokinetics
Toxicity3 years

Countries

Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Germany, Greece, Hong Kong, Israel, Italy, Mexico, New Zealand, Poland, Romania, Singapore, United Kingdom, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026