A Study of BIBW 2992 (Afatinib) in Patients With Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01152437
First received: June 28, 2010
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

This Phase II study is open to patients with metastatic colorectal cancer who have tried but failed chemotherapy regimens containing oxaliplatin and irinotecan. Patients must not have received anti-EGFR (Epidermal Growth Factor Receptor) treatment (for example, cetuximab, panitumumab) in the past. Patients with wild-type KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) colorectal cancer will be randomised to receive either BIBW 2992 or cetuximab. Patients with KRAS mutated colorectal cancer will not be randomised, but will all receive BIBW 2992. The main objectives of the study are: to compare the effectiveness of BIBW 2992 with that of cetuximab in patients with KRAS wild type cancer, and to assess the effectiveness of BIBW 2992 in patients with KRAS mutated cancer.


Condition Intervention Phase
Colorectal Neoplasms
Drug: BIBW 2992
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Partially Randomised Phase II Study to Investigate the Efficacy and Safety of BIBW 2992 in Patients With Metastatic Colorectal Cancer Who Never Received Prior Anti-EGFR (Epidermal Growth Factor Receptor) Treatment

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Percentage of Participants With Objective Response [ Time Frame: Baseline till progression or death, whichever came first, assessed up to 23 months ] [ Designated as safety issue: No ]
    Percentage of participants with objective response: complete response (CR) or partial response (PR) according to RECIST (version 1.1) without confirmation criteria applied.

  • Percentage of Participants With Disease Control (DC) [ Time Frame: Baseline till progression or death, whichever came first, assessed up to 23 months ] [ Designated as safety issue: No ]
    Percentage of participants with objective response or stable disease (SD) as determined by RECIST (version 1.1) with confirmation criteria applied.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Baseline till progression or death, whichever came first, assessed up to 23 months ] [ Designated as safety issue: No ]
    PFS time is defined as time from randomisation (wild-type group) or start of treatment (mutated group) to tumor progression evaluated according to RECIST (version 1.1) or death whichever occurs earlier. Median and confidence interval estimated using product-limit Kaplan-Meier method.

  • Overall Survival (OS) Time [ Time Frame: Baseline till death, assessed up to 23 months ] [ Designated as safety issue: No ]
    OS time is defined as time from the date of randomisation (wild-type group) or date of start of treatment (mutated group) to the date of death. Median and confidence interval estimated using product-limit Kaplan-Meier method.

  • Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 8 (Cpre,ss,8) [ Time Frame: day 8 ] [ Designated as safety issue: No ]
    Cpre,ss,8 represents the pre-dose concentration of afatinib in plasma at steady state on day 8.


Enrollment: 94
Study Start Date: June 2010
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992
Patients receive BIBW 2992 tablets once daily
Drug: BIBW 2992
Patients receive BIBW 2992 tablets once daily, and can reduce dose for adverse event management
Active Comparator: Cetuximab
Patients receive cetuximab intravenously once a week, every week
Drug: Cetuximab
Patients receive cetuximab intravenously, once a week, every week

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Patients with metastatic colorectal cancer who have failed both oxaliplatin- and irinotecan-based regimens
  2. Tumour sample available for KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation testing and other biomarker analyses.

Exclusion criteria:

  1. Prior treatment with Epidermal Growth Factor Receptor (EGFR) targeting small molecules or antibodies.
  2. Biological treatment (including Bevacizumab or any other antiangiogenic agents) during the trial is not allowed.
  3. Known pre-existing interstitial lung disease.
  4. Planned major surgical procedures during the trial period.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01152437

Locations
United Kingdom
1200.74.44001 Boehringer Ingelheim Investigational Site
Bournemouth, United Kingdom
1200.74.44005 Boehringer Ingelheim Investigational Site
Bristol, United Kingdom
1200.74.44006 Boehringer Ingelheim Investigational Site
Cambridge, United Kingdom
1200.74.44003 Boehringer Ingelheim Investigational Site
Glasgow, United Kingdom
1200.74.44009 Boehringer Ingelheim Investigational Site
London, United Kingdom
1200.74.44012 Boehringer Ingelheim Investigational Site
Manchester, United Kingdom
1200.74.44007 Boehringer Ingelheim Investigational Site
Northwood, United Kingdom
1200.74.44013 Boehringer Ingelheim Investigational Site
Nottingham, United Kingdom
1200.74.44011 Boehringer Ingelheim Investigational Site
Poole, United Kingdom
1200.74.44010 Boehringer Ingelheim Investigational Site
Sheffield, United Kingdom
1200.74.44008 Boehringer Ingelheim Investigational Site
Southampton, United Kingdom
1200.74.44004 Boehringer Ingelheim Investigational Site
Sutton, Surrey, United Kingdom
1200.74.44002 Boehringer Ingelheim Investigational Site
Truro, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01152437     History of Changes
Other Study ID Numbers: 1200.74, 2009-011996-59
Study First Received: June 28, 2010
Results First Received: August 8, 2013
Last Updated: May 27, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014