A Biomarker Identification Trial of Tarceva (Erlotinib) in Patients With Advanced Pancreatic Cancer

A Phase II Biomarker Identification Trial for Erlotinib (Tarceva®) in Patients With Advanced Pancreatic Carcinoma

This study is designed to identify biomarkers which may predict improvement in progression free survival from treatment with Tarceva, in patients with advanced pancreatic cancer who failed one prior regimen of standard chemotherapy or who are deemed unsuitable for chemotherapy. It will also assess the efficacy and safety of Tarceva in this patient population. Patients will be randomized to receive either Tarceva 150mg/day po, or placebo po daily. Tumor tissue will be used for biomarker analysis. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Erlotinib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
    • St. Leonards, New South Wales, Australia, 2065
    • Sydney, New South Wales, Australia, 2076
  • Victoria
    • Box Hill, Victoria, Australia, 3128
• Brazil
  • BA
    • Salvador, Bahia, BA, Brazil, 40170-380
  • MG
    • Belo Horizonte, MG, Brazil, 30110-0090
  • PR
    • Curitiba, PR, Brazil, 81520-060
  • RS
    • Ijui, RS, Brazil, 98700-000
    • Porto Alegre, RS, Brazil, 90430-090
    • Porto Alegre, RS, Brazil, 91350-200
    • Porto Alegre, RS, Brazil, 90020-090
  • SP
    • Jau, SP, Brazil, 17210-080
    • Sao Paulo, SP, Brazil, 01246-000
    • Sao Paulo, SP, Brazil, 05652-000
• Bulgaria
  • Gabrovo, Bulgaria, 5300
  • Pleven, Bulgaria, 5800
  • Plovdiv, Bulgaria, 4004
  • Sofia, Bulgaria, 1756
  • Sofia, Bulgaria, 1233
  • Sofia, Bulgaria, 1431
  • Vratsa, Bulgaria, 3000
  • Vratza, Bulgaria, 3000
• Croatia
  • Zagreb, Croatia, 10000
• Germany
  • Bochum, Germany, 44791
  • Dresden, Germany, 01307
  • Esslingen, Germany, 73730
  • Greifswald, Germany, 17489
  • Hamburg, Germany, 20148
  • Köln, Germany, 50937
  • Saarbruecken, Germany, 66113
  • Ulm, Germany, 89081
• Hong Kong
  • Hong Kong, Hong Kong
  • Hong Kong, Hong Kong, 852
• India
  • Bangalore, India, 560029
  • Chennai, India, 600035
  • Jaipur, India, 302004
  • Kochi, India, 682304
  • Kolkata, India, 700053
  • Ludhiana, India, 141 001
  • Mumbai, India, 400012
  • New Delhi, India, 110076
  • Pune, India, 411 001
  • Vellore, India, 632004
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
• Latvia
  • Riga, Latvia, LV-1002
• Lithuania
  • Kaunas, Lithuania, 50009
  • Vilnius, Lithuania, 08660
  • Vilnius, Lithuania, 08661
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
  • Penang, Malaysia, 11200
• Mexico
  • Monterrey, Mexico, 64020
• Peru
  • Arequipa, Peru, 04001
  • Chiclayo, Peru, CIX
  • San Isidro, Peru, L27 Lima
• Romania
  • Bucharest, Romania
  • Cluj Napoca, Romania, 400015
  • Craiova (Dolj county), Romania, 200535
• Russian Federation
  • Irkutsk, Russian Federation, 664035
  • Kazan, Russian Federation, 420111
  • Krasnodar, Russian Federation, 350040
  • Moscow, Russian Federation, 115478
  • St Petersburg, Russian Federation, 195067
  • St Petersburg, Russian Federation, 198255
• Singapore
  • Singapore, Singapore, 169610
• Slovenia
  • Ljubljana, Slovenia, 1000
• Ukraine
  • Kiev, Ukraine, 36022
• United Kingdom
  • London, United Kingdom, SE1 9RT
  • London, United Kingdom, N18 1QX
  • London, United Kingdom, SW3 6JJ
  • London, United Kingdom, EC1A 7BE
  • Sutton, United Kingdom, SM2 5PT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients, >=18 years of age;
• histologically or cytologically documented locally advanced-unresectable or metastatic pancreatic cancer;
• measurable disease according to RECIST;
• failure of at least one prior chemotherapy regimen, or who are deemed unsuitable for chemotherapy;
• ECOG performance status of 0-2.

Exclusion Criteria:

• local or locally advanced-resectable pancreatic cancer;
• any other malignancies within last 5 years, except for adequately treated cancer in situ of the cervix, or basal or squamous cell skin cancer;
• major surgery within 2 weeks prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib; Participants with advanced pancreatic carcinoma with Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 2, who had failed 1 prior regimen of chemotherapy or who were considered unsuitable for chemotherapy, received erlotinib 150 mg orally once daily until disease progression, unacceptable toxicity, withdrawal, or death.	Drug: Erlotinib; Participants received erlotinib 150 mg tablet orally once daily.; Other Names: Tarceva
Placebo Comparator: Placebo; Participants with advanced pancreatic carcinoma with ECOG PS score of 0 to 2, who had failed 1 prior regimen of chemotherapy or who were considered unsuitable for chemotherapy, received placebo matching to erlotinib 150 mg tablet orally once daily until disease progression, unacceptable toxicity, withdrawal, or death.	Drug: Placebo; Participants received placebo matching to erlotinib 150 mg tablet orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Progression-free survival (PFS) was defined as the time from the date of randomization to the date of the first occurrence of PD or death whichever occurred first. Participants without event were censored at the date of last tumor assessment where non-progression was documented. Analysis was performed using Kaplan-Meier method.	From the time of randomization until progression of disease or death (up to 30 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Best Overall Response Rate	Response rate was defined as Complete Response (CR) or Partial Response (PR), according to response evaluation criteria in solid tumors (RECIST) Version 1.0 criteria, for at least 4 weeks at any time during randomized treatment (confirmed response). CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions.	From the time of randomization until progression of disease or death (up to 30 months)
Percentage of Participants With Disease Control Rate (DCR)	Disease control rates (DCR) were measured according to RECIST Version 1.0 criteria. Disease control was defined as being a responder or as having stable disease for at least 6 weeks post-randomization. Stable disease was defined as having neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.	Randomization to Clinical Cutoff: 20 December 2010 (up to 30 months)
Overall Survival	Overall survival was defined as the time from the date of randomization to the date of death, regardless of the cause of death.	From the time of randomization until or death (up to 30 months)
Number of Participants With Adverse Events (AEs)	An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a study treatment, regardless of whether or not the event had a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.	Up to 28 days after discontinuation of study drug (up to 30 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Propper D, Davidenko I, Bridgewater J, Kupcinskas L, Fittipaldo A, Hillenbach C, Klughammer B, Ducreux M. Phase II, randomized, biomarker identification trial (MARK) for erlotinib in patients with advanced pancreatic carcinoma. Ann Oncol. 2014 Jul;25(7):1384-1390. doi: 10.1093/annonc/mdu176. Epub 2014 May 14.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: April 30, 2008
• First Submitted That Met QC Criteria: May 7, 2008
• First Posted (Estimate): May 8, 2008

Study Record Updates

• Last Update Posted (Estimate): June 17, 2016
• Last Update Submitted That Met QC Criteria: May 13, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: BO21129; 2007-003738-40 (EudraCT Number)