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
- 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
- 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
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.
Primary Purpose: Treatment
Maximum tolerated dose of erlotinib hydrochloride (Phase I)
Mercedes Porosnicu, MD
Comprehensive Cancer Center of Wake Forest University
United States: Institutional Review Board
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|UNC Linberger Comprehensive Cancer Center||Chapel Hill, North Carolina 27599|