Everolimus, Erlotinib Hydrochloride, and Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer Previously Treated With Radiation Therapy
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Salivary Gland Squamous Cell Carcinoma
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
Other: immunohistochemistry staining method
Genetic: polyacrylamide gel electrophoresis
Other: pharmacological study
Radiation: external beam radiation therapy
Genetic: microarray analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation Study of the mTOR Inhibitor Everolimus (RAD001) and Erlotinib Concurrently With Radiation Therapy in the Re-Irradiation Setting for Head and Neck Cancer|
- MTD of RAD001, erlotinib and radiotherapy in the re-irradiation setting [ Time Frame: During the period of radiation treatment or within the first 2 weeks after the completion of radiotherapy ] [ Designated as safety issue: Yes ]Establish the safety profile of this regimen and establish the MTD of RAD001 with/without erlotinib in conjunction with RT.
- Preliminary data on response rate [ Time Frame: At 5 and 13 weeks post-radiation therapy and then every 3 months until disease progression or until patient comes off study ] [ Designated as safety issue: No ]Overall response rate will be estimated with its 95% confidence interval by dose level and will be compared with historical data and our own extensive experience at Fox Chase. Response will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Overall survival [ Time Frame: every 6 months ] [ Designated as safety issue: No ]Overall survival will be estimated using Kaplan-Meier curves and will be compared with historical data and our own extensive experience at Fox Chase.
- Biological features of recurrent or second primary tumors, as well as surrogates of mTOR, EGFR and HIF-1α inhibition [ Time Frame: At baseline and week 4 ] [ Designated as safety issue: No ]Correlative assessment of biomarkers as well as surrogates of response will be performed. Biological endpoints (protein expression of EGFR, pEGFR, EGFR amplification, Akt/pAkt, PS6Kinase, HIF-1 α and its associated hypoxia induced angiogenesis-associated genes) will use linear or nonlinear mixed models, as appropriate. Associations between study drug dose and biological endpoints will be similarly analyzed.
|Study Start Date:||April 2011|
|Study Completion Date:||May 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor and radiation therapy)
Patients receive RAD001 PO and erlotinib hydrochloride PO QD. Treatment continues for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo EBRT BID 5 days a week for 5 weeks.
Other Names:Drug: erlotinib hydrochloride
Other Names:Procedure: biopsy
Other Name: biopsiesOther: laboratory biomarker analysis
Correlative studiesOther: immunohistochemistry staining method
Other Name: immunohistochemistryGenetic: polyacrylamide gel electrophoresis
Other Name: electrophoresis, polyacrylamide gelOther: pharmacological study
Other Name: pharmacological studiesRadiation: external beam radiation therapy
Other Name: EBRTGenetic: microarray analysis
Other Name: gene expression profiling
I. To establish the maximum tolerated dose (MTD) and safety of RAD001 given concurrently with external beam radiation therapy (EBRT) in the re-irradiation setting for head and neck cancer.
I. Obtain preliminary data on response rate. II. Determine progression-free survival at 6 and 12 months and overall survival.
III. Perform correlative studies to evaluate and characterize biological features of recurrent or second primary tumors, as well as to follow surrogates of mammalian target of rapamycin (mTOR), epidermal growth factor receptor (EGFR) and hypoxia-inducible factor 1-alpha (HIF-1α) inhibition.
OUTLINE: This is a dose-escalation study of everolimus and erlotinib hydrochloride.
Patients receive RAD001 orally (PO) and erlotinib hydrochloride PO once daily (QD). Treatment continues for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo EBRT twice daily (BID) 5 days a week for 5 weeks.
After completion of study treatment, patients are followed up for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01332279
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111|