A Study of RO5083945 in Combination With Cisplatin and Gemcitabine or Carboplatin and Paclitaxel in Patients With Advanced or Recurrent Non-Small Cell Lung Cancer of Squamous Histology Who Have Not Received Prior Chemotherapy for The Metastatic Disease

Study Overview
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Brief Summary
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This open-label, multicenter, non-randomized, dose-escalating phase Ib study with an expansion cohort will determine the recommended Phase II dose and schedule to investigate safety, tolerability, and activity of RO5083945 in combination with cisplatin and gemcitabine or carboplatin and paclitaxel in patients with advanced or recurrent non-small cell lung cancer of squamous histology who have not received prior chemotherapy for the metastatic disease. Cohorts of patients will receive escalating doses of RO5083945 in combination with up to 6 cycles of cisplatin and gemcitabine or carboplatin and paclitaxel. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Official Title
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A MULTICENTER, OPEN-LABEL PHASE IB STUDY OF RO5083945 IN COMBINATION WITH CISPLATIN AND GEMCITABINE OR CARBOPLATIN AND PACLITAXEL IN PATIENTS WITH ADVANCED OR RECURRENT NON SMALL CELL LUNG CANCER OF SQUAMOUS HISTOLOGY WHO HAVE NOT RECEIVED PRIOR CHEMOTHERAPY FOR THE METASTATIC DISEASE.

Conditions
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Non-Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: RO5083945
* Drug: carboplatin
* Drug: cisplatin
* Drug: gemcitabine
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age Locally advanced (stage IIIB, excluding patients who are candidates for chemo-radiotherapy or radical thoracic radiotherapy), metastatic (stage IV) or recurrent squamous non-small cell lung cancer (NSCLC) Histologically documented squamous NSCLC. Mixed tumors should be categorized according to the predominant cell type Histological tumor tissue sample from initial diagnosis or new tumor biopsy representative of the disease Patients who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 3 months prior to enrollment At least one measurable disease lesion as per RECIST 1.1 criteria Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Adequate hematological, liver and renal function Females of childbearing potential must commit to using a reliable and appropriate method of contraception until at least 3 months after the end of the last dose of study treatment Exclusion Criteria: Prior chemotherapy (excluding neoadjuvant/adjuvant chemotherapy/chemo-radiotherapy) or treatment with another systemic anti-cancer agent (e.g. monoclonal antibody, tyrosine kinase inhibitor) Radiotherapy within the last 4 weeks prior to first dosing, except for limited field palliative radiotherapy for bone pain relief Treatment with any other investigational agent within 30 days prior to starting study treatment or participation in another clinical trial (e.g. CTC blood collection) within 7 days prior to starting study treatment Historical or clinical evidence of central nervous system (CNS) metastases (except for previously treated CNS metastases in patients that are asymptomatic, have had no evidence of active CNS metastases for >/= 3 months prior to first dose and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days) Recent history of poorly controlled hypertension (systolic >180 mmHg or diastolic >100 mmHg) Severe uncontrolled illness, including poorly controlled diabetes mellitus and active or uncontrolled infection Hypersensitivity to the active substance or to any excipients or to any of the study drugs including premedication (corticosteroids, anti-histamine, paracetamol) Pregnant or breastfeeding women

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RO5083945 + carboplatin + paclitaxel<br> | Drug: RO5083945<br>* multiple ascending doses<br>Drug: carboplatin<br>* up to 6 cycles<br>Drug: paclitaxel<br>* up to 6 cycles<br>|
| Experimental: RO5083945 + cisplatin +gemcitabine<br> | Drug: RO5083945<br>* multiple ascending doses<br>Drug: cisplatin<br>* up to 6 cycles<br>Drug: gemcitabine<br>* up to 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose in combination with cisplatin and gemcitabine or carboplatin and paclitaxel |  | approximately 1.5 years | 
| Recommended phase II dose (RP2D) of RO5083945 in combination with cisplatin and gemcitabine or carboplatin and paclitaxel |  | approximately 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | approximately 1.5 years | 
| Pharmacokinetics: Serum concentrations of RO5083945 in combination with cisplatin and gemcitabine or carboplatin and paclitaxel |  | up to 18 weeks | 
| Pharmacokinetics: Effect of RO5083945 on serum concentrations of cisplatin |  | up to 18 weeks | 
| Pharmacokinetics: Effect of RO5083945 on serum concentrations of gemcitabine |  | up to 18 weeks | 
| Pharmacokinetics: Effect of RO5083945 on serum concentrations of carboplatin |  | up to 18 weeks | 
| Pharmacokinetics: Effect of RO5083945 on serum concentrations of paclitaxel |  | up to 18 weeks | 
| Preliminary evidence of antitumor activity: Objective response rate (complete response, partial response and stable disease) |  | approximately 1.5 years | 
| Duration of response |  | approximately 1.5 years | 
| Biomarker assessments : Immune effector cells/EGFR markers |  | up to 18 weeks |