An Exploratory Study of RO4929097 in Patients With Recurrent or Refractory Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This study will evaluate the anti-tumour activity, safety and tolerability of RO4929097 as monotherapy in patients with recurrent or refractory non-small cell lung cancer. Patients will receive oral doses of RO4929097 of 80mg (cohort 1) or recommended Phase II dose (cohort 2) on a 3 days on 4 days off schedule. Anticipated time on study treatment is until disease progression or unacceptable toxicity. Target sample size is <50.

Official Title
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An Exploratory Study on Anti-tumour Activity of Orally Administered RO4929097, a Gamma-secretase Inhibitor, as a Single Agent in Patients With Recurrent or Refractory Non-Small Cell Lung Cancer (NSCLC).

Conditions
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Non-Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: RO4929097
* Drug: RO4929097


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >/= 18 years of age stage IIIB/IV recurrent or refractory non-small cell lung cancer at most 2 lines of prior therapy in the metastatic setting (first line: platinum containing regimen and bevacizumab; second line: EGFR-targeted therapy) ECOG performance status 0-2 adequate liver, renal and bone marrow function Exclusion Criteria: prior chemotherapy or radiotherapy </= 4 weeks before first dose of study drug history of other malignancy within the past 2 years, except for basal cell skin carcinoma or in situ cervical carcinoma history of CNS metastases or leptomeningeal metastases, except for clinically stable disease serious cardiovascular illness

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort 1<br> | Drug: RO4929097<br>* 80mg po daily, 3 days on 4 days off schedule<br>|
| Experimental: cohort 2<br> | Drug: RO4929097<br>* recommended phaseII dose, orally once daily, 3 days on 4 days off schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumour blood flow and tumour metabolic response rate |  | PET and CT assessments on day 4 (cycle 1) and day 16 (cycles 1 and 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile and pharmacodynamic parameters (e.g. changes in circulating endothelial and hematopoietic precursors) |  | pharmacokinetics: cycle 1 on days 1, 2, 4, 10, 11, 16; cycle 2 on days 1, 2, 16\npharmacodynamics: cycle 1 on days 1, 2, 4, 11, 16; cycle 2 on days 1, 16 | 
| Tumour response according to RECIST criteria |  | assessments once every 2nd cycle on day 16 | 
| Safety and tolerability: AEs, laboratory parameters |  | throughout study, laboratory assessments on days 1, 8 and 15 of each cycle |