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

• ClinicalTrials.gov Identifier: NCT00026338
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: April 2, 2020
• Sponsor: NCIC Clinical Trials Group
• Information provided by (Responsible Party): Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Tracking Information

• First Submitted Date: November 9, 2001
• First Posted Date: January 27, 2003
• Last Update Posted Date: April 2, 2020
• Actual Study Start Date: October 29, 2001
• Actual Primary Completion Date: September 17, 2004 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 28, 2011): Overall survival [ Time Frame: 3 years ]
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: September 28, 2011)

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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Gemcitabine With/Out Erlotinib in Unresectable Locally Advanced/Metastatic 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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• 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)

Study Arms

• Active Comparator: OSI-774 plus Gemcitabine
  Interventions:

  • Drug: erlotinib hydrochloride
  • Drug: gemcitabine hydrochloride
• Active Comparator: Placebo plus gemcitabine
  Intervention: Drug: gemcitabine hydrochloride

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. 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 28, 2011): 569
• Original Enrollment: Not Provided
• Actual Study Completion Date: February 10, 2009
• Actual Primary Completion Date: September 17, 2004 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Germany, Greece, Hong Kong, Israel, Italy, Mexico, New Zealand, Poland, Romania, Singapore, United Kingdom, United States

Administrative Information

• NCT Number: NCT00026338
• Other Study ID Numbers: PA3; CAN-NCIC-PA3 ( Other Identifier: PDQ ); OSI-CAN-NCIC-PA3 ( Other Identifier: OSI ); CDR0000069020 ( Other Identifier: PDQ )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Canadian Cancer Trials Group ( NCIC Clinical Trials Group )
• Study Sponsor: NCIC Clinical Trials Group
• Collaborators: Not Provided

Investigators

• Study Chair: Malcolm J. Moore, MD; Princess Margaret Hospital, Canada

• PRS Account: Canadian Cancer Trials Group
• Verification Date: March 2020