Phase I/II Clinical Trial of Combined Re-Irradiation With Pemetrexed and Erlotinib Followed by Maintenance Erlotinib for Recurrent and Second Primary Squamous Cell Carcinoma of the Head and Neck
I. Evaluate acute toxicity and feasibility of the combined re-irradiation with
radiosensitizing drugs pemetrexed (pemetrexed disodium) and erlotinib (erlotinib
hydrochloride). (Phase I) II. Determine maximum tolerated dose (MTD) for erlotinib,
recommended for the phase II portion of the study. (Phase I) III. Determine progression free
survival at 1 year. (Phase II)
I. Median progression free survival, median overall survival and overall survival at 1 year
and at 2 years.
II. Objective tumor response measured by computed tomography (CT) scan or magnetic resonance
III. Evaluate acute and chronic toxicity of the combined re-irradiation with
radiosensitizing drugs pemetrexed and erlotinib.
IV. Measure quality of life (QOL) by standard survey forms: Functional Assessment of Cancer
Therapy-Head and Neck (FACT-H&N), Performance Status Scale for Head and Neck Cancer Patients
(PSS-HN), and swallowing by direct functional measurements and by Scale for
Dysphagia-Related Outcomes Quality of Life (SWAL-QOL) survey at different time points to
evaluate the impact of treatment on QOL.
V. Biomarkers evaluation by nano liquid chromatography-tandem mass spectrometry (LC-MS/MS)
in tumor tissue, reported to normal tissue, the level of phosphorylation of different
tyrosine residues within the cytoplasmic domain of epidermal growth factor receptor (EGFR),
bound adaptors, as well as markers of downstream pathways activation and corroborate with
level of phosphor (P)-AKT and phosphor-extracellular signal-regulated kinases (P-ERK)
evaluated by immunohistochemistry and with response to treatment. Measure level of
thymidylate synthase (TS) and P53 and corroborate with treatment response.
OUTLINE: This is a phase I, dose-escalation study of erlotinib hydrochloride followed by a
phase II study.
Patients undergo intensity modulated radiotherapy (IMRT) once daily, 5 days a week, for 6
weeks. Patients receive pemetrexed disodium intravenously (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 erlotinib
hydrochloride orally (PO) once daily (QD) beginning on day 1 of radiotherapy and continuing
for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 1 year, and then annually thereafter.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of erlotinib hydrochloride, based on incidence of dose limiting toxicities (DLT) (phase I)
DLT is defined as grade IV mucositis or dermatitis lasting more than 3 days, or grade III or IV mucositis lasting longer than 6 weeks or longer from the completion of therapy, or any other grade III or IV toxicity, regardless of duration and which do not respond to treatment or need to delay treatment for more than 2 weeks because of any type of toxicity during the re-irradiation segment of the treatment.
Up to 6 weeks after completion of therapy
Comprehensive Cancer Center of Wake Forest University
United States: Institutional Review Board
|University of North Carolina||Chapel Hill, North Carolina 27599|
|Wake Forest University Health Sciences||Winston-Salem, North Carolina 27157|