Everolimus, Carboplatin, and Etoposide in Treating Patients With Small Cell Lung Cancer or Other Advanced Solid Tumors
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with everolimus may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of everolimus, carboplatin, and etoposide in treating patients with small cell lung cancer or other advanced solid tumors.
|Lung Cancer Unspecified Adult Solid Tumor, Protocol Specific||Drug: Carboplatin Drug: Etoposide Drug: RAD001||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Carboplatin and Etoposide in Combination With Everolimus (RAD001) in Advanced Solid Tumors, With Emphasis on Small Cell Lung Cancer (SCLC)|
- Safety and feasibility of combining RAD001 with carboplatin and etoposide in advanced solid tumors, with emphasis on SCLC. [ Time Frame: Up to 1 year from start of treatment ]
- Maximum-tolerated dose as assessed by NCI CTCAE, Version 3.0 [ Time Frame: April 2011 ]
- Dose-limiting toxicities and toxicity profile as assessed by NCI CTCAE, Version 3.0 [ Time Frame: Up to one year. ]
- Preliminary efficacy of this regimen in patients with small cell lung cancer [ Time Frame: Up to one year ]
- Pharmacokinetic parameters [ Time Frame: Up to one year ]
- Exploratory biomarker analysis [ Time Frame: Up to one year ]
|Actual Study Start Date:||March 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Experimental: Phase I Dose-Escalation
This is a phase I dose escalation study of RAD001 and carboplatin/etoposide. Patients will be accrued in a standard 3 + 3 design based on toxicities experienced during the first cycle. Ten additional chemotherapy naive extensive stage small cell lung cancer (ES-SCLC) patients will be accrued at the Maximum Tolerated Dose (MTD) for further toxicity and response assessment.
Intravenous (IV) on Day 1 of each 21-day cycle, as per dose escalation schedule (dose levels 1 and 2: dose levels 3 and 4). Number of cycles: 6 maximum.
Other Name: ParaplatinDrug: Etoposide
80mg/m2, Intravenous on Days 1, 2, 3 of a 21-day cycle (all dose levels). Number of cycles: 6 maximum.
Other Names:Drug: RAD001
Orally on Days 1-21 of a 21-day cycle, as per dose escalation schedule (dose level 1: 2.5 mg, dose level 2: 5 mg, dose level 3: 5.0 mg, and dose level 4: 10.0 mg). Number of cycles: unlimited (drug taken from Day 1 until progression of disease or unacceptable toxicity).
- Determine the safety and feasibility of everolimus combined with carboplatin and etoposide in patients with advanced solid tumors, with emphasis on small cell lung cancer (SCLC).
- Determine the maximum-tolerated dose of this regimen in these patients.
- Describe the dose-limiting toxicities and toxicity profile associated with this regimen in these patients.
- Determine, preliminarily, the efficacy of this regimen in an expanded cohort of patients with SCLC.
- Assess the pharmacokinetic parameters of everolimus in this combination.
OUTLINE: This is a dose-escalation study.
Patients receive oral everolimus on days 1-21, carboplatin IV over 15-30 minutes on day 1, and etoposide IV over 30 minutes on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients in the expanded cohort undergo blood collection on days 1, 15, and 22 for pharmacokinetic studies by liquid chromatography-tandem mass spectrometry.
After completion of study therapy, patients are followed for 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00807755
|United States, California|
|University of California Davis Cancer Center|
|Sacramento, California, United States, 95817|
|Principal Investigator:||David Gandara, MD||University of California School of Medicine - Davis|