Everolimus, Erlotinib Hydrochloride, and Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer Previously Treated With Radiation Therapy
|ClinicalTrials.gov Identifier: NCT01332279|
Recruitment Status : Withdrawn (Pharmaceutical co. withdrew support. Study was never activated and did not accrue any patients.)
First Posted : April 11, 2011
Last Update Posted : March 3, 2016
|Condition or disease||Intervention/treatment||Phase|
|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 Tongue Cancer||Drug: everolimus Drug: erlotinib hydrochloride Procedure: biopsy Other: laboratory biomarker analysis Other: immunohistochemistry staining method Genetic: polyacrylamide gel electrophoresis Other: pharmacological study Radiation: external beam radiation therapy Genetic: microarray analysis||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||April 2011|
|Primary Completion Date :||May 2011|
|Study Completion Date :||May 2011|
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
- 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 ]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 ]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 ]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 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01332279
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111|