Everolimus, Carboplatin, and Paclitaxel in Locally Advanced Head and Neck Cancer That Cannot Be Removed by Surgery

Phase 1

Completed

• Conditions: Head and Neck Cancer
• Interventions: Drug: carboplatin; Drug: RAD001; Drug: paclitaxel

• Registration Number: NCT01333085
• Lead Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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)

Secondary

* 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.

Study Timeline

• Study Start: 2009-10
• Study First Submitted: 2011-04-08
• Study First Submitted QC: 2011-04-08
• Study First Posted: 2011-04-11
• Status Verified: 2013-03
• Primary Completion: 2013-03
• Study Completion: 2013-05
• Last Update Submitted: 2016-02-09
• Last Update Posted: 2016-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RAD001-paclitaxel-carboplatin	RAD001	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
RAD001-paclitaxel-carboplatin	carboplatin	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
RAD001-paclitaxel-carboplatin	paclitaxel	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

Primary Outcome Measures

Name	Time	Method
objective response rate	9 weeks	To access the objective response rate of the combination RAD001-carboplatin-Paclitaxel according the the RECIST criteria, after 9 weekly cycles (phase II)
Maximum tolerated dose	weekly	to determine the maximum tolerated dose (MTD) and recommended dose of weekly RAD001 in combination with carboplatin and paclitaxel (phase I)

Trial Locations

Locations (5)

Hopital Beaujon; 🇫🇷 Clichy, France

Centre Léon Berard; 🇫🇷 Lyon, France

Institut Curie; 🇫🇷 Paris, France

Hôpital Privé Saint Joseph; 🇫🇷 Paris, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France