Everolimus, Carboplatin, and Paclitaxel in Locally Advanced Head and Neck Cancer That Cannot Be Removed by Surgery (CAPRA)
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 paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I/II trial is studying the side effects and best dose of giving everolimus together with carboplatin and paclitaxel in treating patients with locally advanced head and neck cancer that cannot be removed by surgery.
Head and Neck Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Induction Chemotherapy With Weekly RAD001, Carboplatin and Paclitaxel in Unresectable or Inoperable Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)|
- Maximum tolerated dose [ Time Frame: weekly ] [ Designated as safety issue: Yes ]to determine the maximum tolerated dose (MTD) and recommended dose of weekly RAD001 in combination with carboplatin and paclitaxel (phase I)
- objective response rate [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]To access the objective response rate of the combination RAD001-carboplatin-Paclitaxel according the the RECIST criteria, after 9 weekly cycles (phase II)
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||May 2013|
|Estimated Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
RAD001: 20,30 or 50 mg PO 9 weekly cycles Paclitaxel: 60 mg/m²IV, in 1 hour, 9 weekly cycles Carboplatin AUC2 IV in 1 hour,9 weekly cycles
Other Name: everolimusDrug: paclitaxel
- To determine the maximum-tolerated dose of everolimus when combined with carboplatin and paclitaxel in chemonaïve patients with unresectable or inoperable locally advanced head and neck squamous cell carcinoma. (Phase I)
- To determine the safety profile of weekly everolimus in combination with carboplatin and paclitaxel in chemonaïve patients with unresectable or inoperable locally advanced head and neck squamous cell carcinoma. (Phase I)
- To determine the anti-tumor activity of this regimen, in terms of objective response rate of the combination, according to the RECIST criteria in these patients. (Phase II)
- To identify molecular markers of resistance to this regimen in these patients.
- To assess objective response rate before and after completion of radiation therapy in these patients. (Phase II)
OUTLINE: This is a multicenter, phase I dose-escalation study of everolimus followed by a phase II study.
- Phase I: Patients receive paclitaxel IV over 1 hour, carboplatin IV over 1 hour, and escalating doses of oral everolimus on days 1, 8, and 15. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients receive paclitaxel and carboplatin as in phase I and oral everolimus (at a dose determined in the phase I portion of the study) on days 1, 8, and 15. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
After the completion of combination therapy, patients may receive radiotherapy or surgery, at the investigator's discretion.
Blood samples are collected for translational research and molecular markers analysis at baseline and weeks 1, 4, and 9. Tissue samples are collected at baseline and periodically during the study for biomarker and other laboratory analysis.
After completion of study treatment, patients are followed up at 14 days and periodically thereafter.
|Clichy, France, 92110|
|Centre Léon Berard|
|Lyon, France, 69000|
|Hôpital Privé Saint Joseph|
|Paris, France, 75014|
|Paris, France, 75005|
|Institut Claudius Regaud|
|Toulouse, France, 31052|
|Principal Investigator:||Sandrine Faivre||Hopital Beaujon|