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

NCT ID: NCT01333085

Last Updated: 2016-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2013-05-31

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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RAD001-paclitaxel-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

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

RAD001

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

Interventions

carboplatin

Intervention Type: DRUG

RAD001

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

Other Intervention Names

everolimus

Eligibility Criteria

Inclusion Criteria

PRIOR CONCURRENT THERAPY:

• No prior therapy for this cancer
• No prior chemotherapy unless received for treatment of another primary tumor considered in remission
• No prior investigational drug
• More than 30 days since prior participation in another therapeutic trial
• No prior or concurrent radiotherapy (except anterior radiotherapy) unless received for treatment of another primary tumor considered in remission
• No concurrent CYP3A4 strong inhibitors (e.g., azole antimycotics [itraconazole, ketoconazole], HIV protease inhibitor [ritonavir], erythromycin, anti-epileptic drugs [phenytoin, carbamazepine])
• No concurrent anti-coagulant therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GERCOR - Multidisciplinary Oncology Cooperative Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandrine Faivre

Role: PRINCIPAL_INVESTIGATOR

Hopital Beaujon

Locations

Hopital Beaujon

Clichy, , France

Centre Léon Berard

Lyon, , France

Institut Curie

Paris, , France

Hôpital Privé Saint Joseph

Paris, , France

Institut Claudius Regaud

Toulouse, , France

Countries

France

Other Identifiers

FRE-GERCOR-CAPRA

Identifier Type: -

Identifier Source: secondary_id

FRE-GERCOR-O08-1

Identifier Type: -

Identifier Source: secondary_id

EU-21109

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2008-005702-39

Identifier Type: -

Identifier Source: secondary_id

CDR0000698330

Identifier Type: -

Identifier Source: org_study_id