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

Study Overview

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

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.

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.

Pancreatic Cancer

DRUG: erlotinib hydrochloride
DRUG: gemcitabine hydrochloride

PA3
CAN-NCIC-PA3 (OTHER Identifier) (OTHER: PDQ)
OSI-CAN-NCIC-PA3 (OTHER Identifier) (OTHER: OSI)
CDR0000069020 (OTHER Identifier) (OTHER: PDQ)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2001-11-09	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-03-31
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-04-02
First Posted (ACTUAL) 2003-01-27	Results First Posted N/A	Last Verified 2020-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
Triple

Arms and Interventions

Participant Group/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)

Participant Group/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	Measure Description	Time Frame
Overall survival		3 years

Secondary Outcome Measures	Measure Description	Time Frame
Progression free survival		3 years
Quality of Life	Canada, US and selected countries only	3 years
Response rates	Complete and partial response only.	3 years
Toxicity		3 years
EGFR levels	Correlate the expression oftissue EGFR levels (at diagnosis) with outcomes and response to treatment	3 years
Pharmacokinetics	To measure trough levels of081-774 (Tarceva™) to determine population pharmacokinetics	3 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

18 and over

ECOG 0-2

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

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_CHAIR: Malcolm J. Moore, MD, Princess Margaret Hospital, Canada

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General 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.
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, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. doi: 10.1200/JCO.2006.07.9525. Epub 2007 Apr 23.
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, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W. Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2023 Oct 20;41(30):4714-4720. doi: 10.1200/JCO.22.02770.

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