Combination of RAD001 With Carboplatin, Paclitaxel and Bevacizumab in Non-small-cell Lung Cancer (NSCLC) Patients

Study Overview
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Brief Summary
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This 2 step study aims to establish a tolerable dose level and regimen of RAD001 in patients with advanced NCLC not previously treated with systemic therapy. In step 1 of this study, RAD 001 is given in combination with carboplatin and paclitaxel and in Step 2 RAD001 is given in combination with carboplatin, paclitaxel and bevacizumab

Detailed Description
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This is a two-step, open-label, multi-center, dose escalation Phase 1 study in which RAD001 is administered in combination with carboplatin and paclitaxel (CP) in Step 1 as well as carboplatin, paclitaxel, and bevacizumab (CPB) in Step 2 in patients with advanced (unresectable or metastatic) NSCLC not treated previously with systemic therapy for advanced disease

Official Title
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A Two-step Phase 1 Study Investigating the Combination of RAD001 With Carboplatin, Paclitaxel and Bevacizumab in Non-small-cell Lung Cancer (NSCLC) Patients Not Treated Previously With Systemic Therapy

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: RAD001


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age over 18 years Advanced Non Small Cell Lung Cancer (Stage IIIB/IV) Ability to perform normal daily functions Exclusion criteria: Chronic steroid treatment Prior treatment with chemotherapy for advanced lung cancer Prior treatment with mTOR inhibitors Active bleeding conditions, skin conditions, gastrointestinal disorders, mouth ulcers, eye conditions, chronic liver or kidney disorders, uncontrolled diabetes, infections or other severe medical conditions Known sensitivity to platinum compounds, taxanes or bevacizumab Other cancers within the past 5 years Pregnant or breastfeeding women Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 23 Years
Maximum Age: 76 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: Step 1 Arm 1<br>5mg/day RAD001 + Carboplatin + Paclitaxel | Drug: RAD001<br>* 5mg oral tablets of RAD001 - for the 5mg/daily arm, 10mg oral tablets x 3 of RAD001 - for the 30mg/weekly arm<br>* Other names: Everolimus;|
| Experimental: Step 1, Arm 2<br>30mg/week RAD001 + Carboplatin + Paclitaxel | Drug: RAD001<br>* 5mg oral tablets of RAD001 - for the 5mg/daily arm, 10mg oral tablets x 3 of RAD001 - for the 30mg/weekly arm<br>* Other names: Everolimus;|
| Experimental: Step 2, Arm 1<br>5mg/day RAD001 + Carboplatin + Paclitaxel + Bevacizumab | Drug: RAD001<br>* 5mg oral tablets of RAD001 - for the 5mg/daily arm, 10mg oral tablets x 3 of RAD001 - for the 30mg/weekly arm<br>* Other names: Everolimus;|
| Experimental: Step 2, Arm 2<br>30mg/week RAD001 + Carboplatin + Paclitaxel + Bevacizumab | Drug: RAD001<br>* 5mg oral tablets of RAD001 - for the 5mg/daily arm, 10mg oral tablets x 3 of RAD001 - for the 30mg/weekly arm<br>* Other names: Everolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish the feasible doses/regimens of RAD001 in combination with chemotherapy. Primary endpoint is the End-of-cycle DLT rate |  | Ever 3 months or once a critical DLT occurs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative dose intensity (RDI) of Carboplatin + Paclitaxel (step 1) |  | End of step 1 | 
| Relative dose intensity (RDI) of Carboplatin + Paclitaxel + bevacizumab (step 2) |  | End of Step 2 | 
| PK parameters derived from PK profiles of treatment drugs alone and in combination |  | End of Step 1 and Step 2 | 
| Best overall response - measured by CT/MRI scan every 6-8 week |  | Every 6-8 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non Small Cell Lung Cancer, NSCLC, Advanced Lung Cancer, RAD, RAD001, chemotherapy, carboplatin, paclitaxel, bevacizumab