Intensity-Modulated Radiation Therapy, Pemetrexed, and Erlotinib in Treating Patients With Recurrent or Second Primary Head and Neck Cancer
RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs, such as pemetrexed and erlotinib, may make tumor cells more sensitive to radiation therapy. Erlotinib and pemetrexed may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving intensity-modulated radiation therapy together with pemetrexed and erlotinib may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with intensity-modulated radiation therapy and pemetrexed and to see how well they work in treating patients with recurrent or second primary head and neck cancer.
Head and Neck Cancer
Drug: erlotinib hydrochloride
Drug: pemetrexed disodium
Procedure: quality-of-life assessment
Radiation: intensity-modulated radiation therapy
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Phase I/II Clinical Trial of Combined Pre-Irradiation With Pemetrexed and Erlotinib Followed by Maintenance Erlotinib for Recurrent and Second Primary Squamous Cell Carcinoma of the Head and Neck|
- Maximum tolerated dose of erlotinib hydrochloride (Phase I) [ Designated as safety issue: Yes ]
- Progression-free survival (PFS) at 1 year (Phase II) [ Designated as safety issue: No ]
- Median PFS, median overall survival (OS), and OS at 1 and 2 years [ Designated as safety issue: No ]
- Objective tumor response as measured by CT scan or MRI [ Designated as safety issue: No ]
- Toxicity and tolerability [ Designated as safety issue: Yes ]
- Quality of life as measured by speech and swallowing studies and nutrition and pain evaluations [ Designated as safety issue: No ]
- Biomarker predictor of response and tissue prognostic markers [ Designated as safety issue: No ]
|Study Start Date:||March 2008|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
- Evaluate the acute toxicity and feasibility of intensity modulated radiotherapy (IMRT) in combination with radiosensitizing drugs pemetrexed disodium and erlotinib hydrochloride in patients with recurrent or second primary squamous cell carcinoma of the head and neck. (Phase I)
- Determine the maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in these patients. (Phase I)
- Determine progression-free survival (PFS) at 1 year in these patients. (Phase II)
- Determine median PFS, median overall survival (OS), and OS at 1 and 2 years in these patients.
- Determine objective tumor response as measured by CT scan or MRI in these patients.
- Evaluate the acute and chronic toxicity of IMRT in combination with radiosensitizing drugs pemetrexed disodium and erlotinib hydrochloride in these patients.
- Evaluate the impact of treatment on quality of life as measured by FACT-H&N, PSS-HN, MD Anderson Dysphagia Inventory (MDADI), and swallowing by direct functional measurements at different time points.
- Evaluate the level of phosphorylation of different tyrosine residues within the cytoplasmic domain of EGFR, bound adaptors, as well as markers of downstream pathways activation by nano LC-MS/MS in tumor tissue and correlate with levels of P-AKT and P-ERK by immunohistochemistry and with response to treatment.
- Measure the levels of TS and p53 and correlate with treatment response.
OUTLINE: This is a phase I, dose-escalation study of erlotinib hydrochloride followed by a phase II study.
- Phase I: Patients undergo intensity modulated radiotherapy (IMRT) once daily, 5 days a week, for 6 weeks. Patients receive pemetrexed disodium IV over 10 minutes on day 1 of radiotherapy. Treatment with pemetrexed disodium repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral erlotinib hydrochloride once daily beginning on day 1 of radiotherapy and continuing for up to 2 years in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients undergo IMRT and receive pemetrexed sodium as in phase I. Patients also receive erlotinib hydrochloride at the maximum tolerated dose determined in phase I.
Quality of life is assessed at baseline, weekly during treatment, at 1, 6, and 12 months, and then annually thereafter.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.
|United States, North Carolina|
|UNC Linberger Comprehensive Cancer Center||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Dale Flowers, OCN 919-843-9357 email@example.com|
|Wake Forest University Comprehensive Cancer Center||Recruiting|
|Winston-Salem, North Carolina, United States, 27157-1096|
|Contact: Clinical Trials Office - Wake Forest University Comprehensive 336-713-6771|
|Principal Investigator:||Mercedes Porosnicu, MD||Comprehensive Cancer Center of Wake Forest University|
|Principal Investigator:||Kathryn M. Greven, MD||Comprehensive Cancer Center of Wake Forest University|