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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: BIBW 2992
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with metastatic colorectal cancer who have failed both oxaliplatin- and irinotecan-based regimens Tumour sample available for KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation testing and other biomarker analyses. Exclusion criteria: Prior treatment with Epidermal Growth Factor Receptor (EGFR) targeting small molecules or antibodies. Biological treatment (including Bevacizumab or any other antiangiogenic agents) during the trial is not allowed. Known pre-existing interstitial lung disease. Planned major surgical procedures during the trial period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBW 2992<br>Patients receive BIBW 2992 tablets once daily | Drug: BIBW 2992<br>* Patients receive BIBW 2992 tablets once daily, and can reduce dose for adverse event management<br>|
| Active Comparator: Cetuximab<br>Patients receive cetuximab intravenously once a week, every week | Drug: Cetuximab<br>* Patients receive cetuximab intravenously, once a week, every week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response | Percentage of participants with objective response: complete response (CR) or partial response (PR) according to RECIST (version 1.1) without confirmation criteria applied. | Baseline till progression or death, whichever came first, assessed up to 23 months | 
| Percentage of Participants With Disease Control (DC) | Percentage of participants with objective response or stable disease (SD) as determined by RECIST (version 1.1) with confirmation criteria applied. | Baseline till progression or death, whichever came first, assessed up to 23 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | 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. | Baseline till progression or death, whichever came first, assessed up to 23 months | 
| Overall Survival (OS) Time | 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. | Baseline till death, assessed up to 23 months | 
| Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 8 (Cpre,ss,8) | Cpre,ss,8 represents the pre-dose concentration of afatinib in plasma at steady state on day 8. | day 8 |