A Study of RO5083945 in Combination With FOLFIRI Versus FOLFIRI Plus Cetuximab or FOLFIRI Alone as Second Line Treatment in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This randomized, multicenter, open label study will evaluate the safety and efficacy of RO5083945 in combination with FOLFIRI as compared to FOLFIRI plus cetuximab or FOLFIRI alone as second line treatment in patients with metastatic colorectal cancer. Patients will be randomized to receive RO5083945 (1400 mg intravenously on Day 1 and Day 8 and every 2 weeks thereafter) plus FOLFIRI standard iv chemotherapy or FOLFIRI plus cetuximab (400 mg/m2 iv on Day 1 followed by 250 mg/m2 iv every week) or FOLFIRI alone. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Official Title
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A Randomized, Multicenter, Open-label Phase II Study of RO5083945 in Combination With FOLFIRI Versus FOLFIRI Plus Cetuximab or FOLFIRI Alone as Second Line Treatment in Patients With KRAS Wild-type or Mutant Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: FOLFIRI
* Drug: RO5083945
* Drug: cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age Carcinoma of the colon and/or rectum Disease progression during or within 6 months of last dose of oxaliplatin containing first-line combination therapy for metastatic disease ECOG performance status 0-1 Adequate hematological, renal and liver function Exclusion Criteria: Prior treatment with monoclonal antibody/small molecule against epidermal growth factor receptor (EGFR) Prior treatment with irinotecan Radiotherapy within the last 4 weeks before first dose of study drug (except for limited field palliative radiotherapy for bone pain relief) CNS metastasis History of or active autoimmune disorders/conditions

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: KRAS WT A<br> | Drug: FOLFIRI<br>* standard iv chemotherapy<br>Drug: RO5083945<br>* 1400 mg iv on Day 1 and Day 8, and every 2 weeks thereafter<br>|
| Active Comparator: KRAS WT B<br> | Drug: FOLFIRI<br>* standard iv chemotherapy<br>Drug: cetuximab<br>* 400 mg/m2 iv on Day 1, followed by 250 mg/m2 iv every week<br>|
| Experimental: KRAS mutant A<br> | Drug: FOLFIRI<br>* standard iv chemotherapy<br>Drug: RO5083945<br>* 1400 mg iv on Day 1 and Day 8, and every 2 weeks thereafter<br>|
| Active Comparator: KRAS mutant B<br> | Drug: FOLFIRI<br>* standard iv chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival: tumour assessments by CT scan or MRI according to RECIST criteria |  | approximately 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate: tumour assessments by CT scan or MRI according to RECIST criteria |  | approximately 18 months | 
| Duration of response: time from complete or partial response to disease progression or death |  | approximately 18 months | 
| Clinical benefit rate: stable disease for >6 weeks, complete response or partial response; tumour assessments by CT scan or MRI according to RECIST criteria |  | approximately 18 months | 
| Overall survival |  | approximately 18 months | 
| Safety: Incidence of adverse events |  | approximately 18 months | 
| Effect of concomitant FOLFIRI on pharmacokinetics of RO5083945 and vice versa |  | approximately 18 months |