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

Sponsor

GERCOR - Multidisciplinary Oncology Cooperative Group (Other)

Overall Status

Completed

CT.gov ID

NCT01333085

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

9.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: carboplatin Drug: RAD001 Drug: paclitaxel	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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)

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: carboplatin Drug: RAD001 Other Names: everolimus Drug: paclitaxel

Arm

Intervention/Treatment

Experimental: 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

Drug: carboplatin

Drug: RAD001

Other Names:

everolimus

Drug: paclitaxel

Outcome Measures

Primary Outcome Measures

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)
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx
Locally advanced disease (T4 N0-N3 disease)
Unresectable disease OR resectable disease with surgery contra-indication
No stage I, II, III, or IVc disease
Measurable lesions defined as those accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
No known brain metastases (cerebral CT scan is not required if no symptom is present)

PATIENT CHARACTERISTICS:

WHO performance status 0-2
Life expectancy > 3 months
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
Total bilirubin ≤ 1.25 times upper limit of normal (ULN)
Transaminases ≤ 2.5 times ULN
Alkaline phosphatase ≤ 5 times ULN
Creatinine clearance ≥ 60 mL/min
Glycemia ≤ 1.5 times ULN
Cholesterol level ≤ 7.30 mmol/L
Serum total protein normal
Oxygen saturation > 88%
Able to swallow pills
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
No preexisting neuropathy ≥ grade 2
No uncontrolled disease including any of the following:
Diabetes
Hypertension
Symptomatic congestive heart or pulmonary failure
Renal or hepatic chronic disease
Severe infectious disease
No active hemorrhagic syndrome
No prior history of cancer within the past 5 years, except in situ cervical cancer and basal cell skin carcinoma
No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Registration in a national health care system (CMU included)
Not eligible for organ preservation program

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hopital Beaujon	Clichy	France	92110
2	Centre Léon Berard	Lyon	France	69000
3	Institut Curie	Paris	France	75005
4	Hôpital Privé Saint Joseph	Paris	France	75014
5	Institut Claudius Regaud	Toulouse	France	31052