Everolimus and Docetaxel in Treating Patients With Recurrent, Locally Advanced, or Metastatic Head and Neck Cancer

NCT01313390 | Terminated Phase 1 DMC

• 8 other identifiers: CDR0000696702CRUK-UCL-06/053EU-20959ISRCTN-73814534EUDRACT-2007-001951-20CRUK-UCL-CTA-20363/0229/011-00NOVARTIS-CRUK-UCL-06/053AVENTIS-CRUK-UCL-06/053
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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 docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving everolimus together with docetaxel is more effective than giving docetaxel alone in treating patients with head and neck cancer. PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus given together with docetaxel in treating patients with recurrent, locally advanced, or metastatic head and neck cancer.

Conditions

Head and Neck Cancer

Keywords

recurrent squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the larynx; stage III verrucous carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx; stage IV verrucous carcinoma of the larynx; recurrent squamous cell carcinoma of the larynx; recurrent verrucous carcinoma of the larynx; recurrent squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity; recurrent verrucous carcinoma of the oral cavity; stage III verrucous carcinoma of the oral cavity; stage IV verrucous carcinoma of the oral cavity; metastatic squamous neck cancer with occult primary squamous cell carcinoma; recurrent metastatic squamous neck cancer with occult primary; recurrent squamous cell carcinoma of the nasopharynx; stage III squamous cell carcinoma of the nasopharynx; stage IV squamous cell carcinoma of the nasopharynx; recurrent squamous cell carcinoma of the oropharynx; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity; stage III squamous cell carcinoma of the paranasal sinus and nasal cavity; stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity; recurrent salivary gland cancer; salivary gland squamous cell carcinoma; stage III salivary gland cancer; stage IV salivary gland cancer; tongue cancer

Outcome Measures

Primary Outcomes (3)

• Maximum-tolerated dose and recommended phase II dose of everolimus in combination with docetaxel (phase I)

• Safety and tolerability of the combination of everolimus and docetaxel

• Response using RECIST criteria (phase II)

Secondary Outcomes (5)

• Pharmacokinetic profile of docetaxel with and without concurrent everolimus (phase I)

• Pharmacokinetic profile of everolimus with and without concurrent docetaxel (phase I)

• Time to progression following response (time from treatment start to tumor progression as defined by RECIST criteria) (phase II)

• Mutations in EGFR1, AKT, mTOR, ras, or p53 to be tested on paraffin-embedded tissue from the primary or secondary tumor; results to be correlated with outcome (phase II)

• Amplifications of EGFR1 and bcl2 expression to be tested by FISH and immunostaining on paraffin-embedded tissue from primary tumor; results to be correlated with outcome (phase II)

Interventions

docetaxel DRUG

everolimus DRUG

laboratory biomarker analysis OTHER

pharmacological study OTHER

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 head and neck * Locally advanced or metastatic disease * No patients with locally advanced disease for whom radiotherapy is indicated * Recurrent disease * Incurable disease * Measurable disease by RECIST criteria * Recurrent disease within a prior radiation field can be considered to be measurable * Patients may have received 1 line of prior chemotherapy (but not a taxane) for locally advanced or metastatic disease * Patients may have received prior radiation therapy for locally advanced or metastatic disease (but must have completed the radiotherapy \> 6 months before recruitment) * No disease relapsed within 6 months of radiotherapy * No evidence of central nervous system metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Life expectancy ≥ 12 weeks * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 10 g/dL * Urea and creatinine normal * Serum bilirubin normal * AST or ALT ≤ 1.5 times upper limit of normal (ULN) * Alkaline phosphatase \< 2.5 times ULN * Negative pregnancy test * Not pregnant or nursing * Fertile patients must use effective contraception during and for 3 months (female) or 2 months (male) after the last dose of the study treatment * No uncontrolled infection * No mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study * No prior malignancy likely to interfere with the patient's ability to comply with treatment and/or follow up PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior chemotherapy for any cancer, except for head and neck cancer * No prior taxane * No prior therapy with any erbB inhibitors (except cetuximab given with radiotherapy, as indicated in treatment algorithm) * More than 6 months since prior radiotherapy for locally advanced or metastatic disease * At least 4 weeks since prior investigational drug * No concurrent use of drugs known to inhibit CYP3A4 (except dexamethasone), or block P-glycoprotein, including grapefruit juice * No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, or experimental medications * No concurrent live vaccines during everolimus therapy

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

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

UCL Cancer Institute

London, England, WC1E 6DD, United Kingdom

Location

MeSH Terms

Conditions

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

Interventions

Docetaxel; Everolimus

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; Salivary Gland Diseases; Tongue Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Chris Boshoff

  University College London (UCL) Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: March 11, 2011
• Study Start: June 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: December 12, 2011

Record last verified: 2011-12

Locations

GB (1)