A Study of RO5083945 in Combination With Chemotherapy Versus Chemotherapy Alone in Patients With Advanced or Recurrent Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This open label, 2-part study will evaluate the safety and efficacy of RO5083945 in combination with standard chemotherapy in patients with advanced or recurrent non-small cell lung cancer who have not received prior chemotherapy. In Part 1 patients will receive RO5083945 intravenously and standard chemotherapy (cisplatin plus either gemcitabine or pemetrexed) for up to 6 cycles of 3 weeks and then RO5083945 until disease progression. In Part 2 patients will be randomized to receive either RO5083945 in combination with standard chemotherapy or chemotherapy alone for up to 6 cycles. In the absence of disease progression, patients receiving RO503945 can continue treatment with RO5083945 as monotherapy.

Official Title
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A Randomized, Multicenter, Open-label Phase Ib/II Study of RO5083945 in Combination With Cisplatin and Gemcitabine/Pemetrexed Versus Cisplatin and Gemcitabine/Pemetrexed in Patients With Advanced or Recurrent Non Small Cell Lung Cancer Who Have Not Received Prior Chemotherapy

Conditions
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Non-Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: RO5083945
* Drug: cisplatin
* Drug: gemcitabine
* Drug: pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/=18 years of age Advanced (IIIb), metastatic (IV) or recurrent non-small cell lung cancer At least 1 measurable disease lesion as per RECIST criteria Confirmed presence of EGFR in tumor tissue ECOG performance status 0-1 Adequate hematological, renal and liver function Exclusion Criteria: Prior chemotherapy or treatment with another systemic anti-cancer agent Radiotherapy within the last 4 weeks, except for limited field palliative radiotherapy for bone pain relief Symptomatic or active CNS metastases Recent history of poorly controlled hypertension (systolic >180mmHg or diastolic >100mmHg) Requirement for steroids > 40 mg prednisolone

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: A non-squamous<br> | Drug: RO5083945<br>* intravenously, until disease progression<br>Drug: cisplatin<br>* standard treatment, up to 6 cycles<br>Drug: pemetrexed<br>* standard treatment, up to 6 cycles<br>|
| Experimental: A squamous<br> | Drug: RO5083945<br>* intravenously, until disease progression<br>Drug: cisplatin<br>* standard treatment, up to 6 cycles<br>Drug: gemcitabine<br>* standard treatment, up to 6 cycles<br>|
| Active Comparator: B non-squamous<br> | Drug: cisplatin<br>* standard treatment, up to 6 cycles<br>Drug: pemetrexed<br>* standard treatment, up to 6 cycles<br>|
| Active Comparator: B squamous<br> | Drug: cisplatin<br>* standard treatment, up to 6 cycles<br>Drug: gemcitabine<br>* standard treatment, up to 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Progression-free survival, according to RECIST criteria by CT/MRI |  | 23 months | 
| Part 1: Adverse event profile: adverse events, ECG, hematology, urinalysis, human anti-human antibodies (HAHA) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of RO5083945 (AUC, Cmax and Cmin) in combination with cisplatin and gemcitabine/pemetrexed |  | multiple sampling cycles 1-6 (18 weeks) | 
| Duration of response, according to RECIST criteria by CT/MRI |  | from response to disease progression | 
| Clinical benefit rate (complete response, partial response or stable disease for >/=6 weeks), according to RECIST criteria by CT/MRI |  | 23 months | 
| Overall survival |  | 23 months | 
| Overall response rate (ORR), according to RECIST criteria by CT/MRI |  | 23 months |