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

NCT01333085 | Completed Phase 1

• 5 other identifiers: CDR0000698330FRE-GERCOR-CAPRAFRE-GERCOR-O08-1EU-21109EUDRACT-2008-005702-39
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 5

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.

Conditions

Head and Neck Cancer

Keywords

stage IV squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the larynx; stage IV verrucous carcinoma of the larynx; stage IV squamous cell carcinoma of the lip and oral cavity; stage IV verrucous carcinoma of the oral cavity; stage IV squamous cell carcinoma of the oropharynx; tongue cancer

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  to determine the maximum tolerated dose (MTD) and recommended dose of weekly RAD001 in combination with carboplatin and paclitaxel (phase I)

  weekly

• objective response rate

  To access the objective response rate of the combination RAD001-carboplatin-Paclitaxel according the the RECIST criteria, after 9 weekly cycles (phase II)

  9 weeks

Study Arms (1)

RAD001-paclitaxel-carboplatin

EXPERIMENTAL

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; Drug: paclitaxel

Interventions

carboplatin DRUG

RAD001-paclitaxel-carboplatin

RAD001 DRUG

Also known as: everolimus

RAD001-paclitaxel-carboplatin

paclitaxel DRUG

RAD001-paclitaxel-carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead

Study Sites (5)

Hopital Beaujon

Clichy, 92110, France

Location

Centre Léon Berard

Lyon, 69000, France

Location

Institut Curie

Paris, 75005, France

Location

Hôpital Privé Saint Joseph

Paris, 75014, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Tongue Neoplasms

Interventions

Carboplatin; Everolimus; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Mouth Neoplasms; Mouth Diseases; Stomatognathic Diseases; Tongue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Sirolimus; Macrolides; Lactones; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Sandrine Faivre

  Hopital Beaujon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2011
• First Posted: April 11, 2011
• Study Start: October 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: May 1, 2013
• Last Updated: February 10, 2016

Record last verified: 2013-03

Locations

FR (5)