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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00457119

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

8.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: RAD001	Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

69 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Step 1 Arm 1 5mg/day RAD001 + Carboplatin + Paclitaxel	Drug: RAD001 5mg oral tablets of RAD001 - for the 5mg/daily arm, 10mg oral tablets x 3 of RAD001 - for the 30mg/weekly arm Other Names: Everolimus
Experimental: Step 1, Arm 2 30mg/week RAD001 + Carboplatin + Paclitaxel	Drug: RAD001 5mg oral tablets of RAD001 - for the 5mg/daily arm, 10mg oral tablets x 3 of RAD001 - for the 30mg/weekly arm Other Names: Everolimus
Experimental: Step 2, Arm 1 5mg/day RAD001 + Carboplatin + Paclitaxel + Bevacizumab	Drug: RAD001 5mg oral tablets of RAD001 - for the 5mg/daily arm, 10mg oral tablets x 3 of RAD001 - for the 30mg/weekly arm Other Names: Everolimus
Experimental: Step 2, Arm 2 30mg/week RAD001 + Carboplatin + Paclitaxel + Bevacizumab	Drug: RAD001 5mg oral tablets of RAD001 - for the 5mg/daily arm, 10mg oral tablets x 3 of RAD001 - for the 30mg/weekly arm Other Names: Everolimus

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

23 Years to 76 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgetown University/Lombardi Cancer Center StudyCoordinator:CRAD001C2114	Washington	District of Columbia	United States	20007-2197
2	LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center	New Orleans	Louisiana	United States	70115
3	U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office	Dallas	Texas	United States	75390-9151
4	MD Anderson Cancer Center/University of Texas Thoractic Head/Neck Med. Onc.	Houston	Texas	United States	77030-4009
5	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
6	Novartis Investigative Site	Heidelberg	Victoria	Australia	3084
7	Novartis Investigative Site	Essen		Germany	45122
8	Novartis Investigative Site	Heidelberg		Germany	69126