A Phase I Study of OSI-774 in Combination With Standard Fractionation Radiation Therapy in Patients With Oral Cavity or Oropharyngeal Cancer Stage II or III and in Combination With Standard Fractionation Radiation Therapy and Low Dose Daily Cisplatin in Patients With Oral Cavity or Oropharyngeal Cancer Stage III and IV
I. Determination of the maximally tolerated dose (MTD) of the combination of daily oral
OSI-774 and standard fractionation external beam radiation therapy in patients with oral
cavity (OC) or oropharyngeal (OP) squamous cell carcinoma (SCC), stage II and III.
II. Determination of the MTD of daily oral OSI-774, low dose daily cisplatin at 6 mg/m^2/day
and standard fractionation external beam radiation therapy in patients with oral cavity or
oropharyngeal SCC stage III and IV.
III. Determination of the safety of chronic oral dosing of OSI-774 after radiation therapy.
I. Determination of biological markers of activity of OSI-774 in tumor biopsy specimens from
patients with SCC of OC and OP pre and post therapy.
II. Determination of the ability of (18F)-FDG-PET scan to demonstrate biological activity of
OSI-774 in previously untreated patients with SCC of the OC and OP and to predict for
OUTLINE: This is a multicenter, dose-escalation study of erlotinib. Patients are assigned to
1 of 2 regimens according to disease stage.
Regimen A (patients with stage II [T2, N0] or III [T1-2, N1] disease): Patients receive oral
erlotinib once daily. Beginning on day 15, patients also undergo intensity-modulated
radiotherapy (IMRT) once daily 5 days a week for 7 weeks.
Regimen B (patients with stage III [T3, N0-1] or IV [T1-4, N2-3, M0 or T4, N0-1, M0]
disease): Patients receive oral erlotinib and undergo IMRT as in regimen A. Patients also
receive cisplatin IV over 20 minutes on each day of radiotherapy.
Patients in both regimens continue to receive erlotinib until the last day of IMRT (patients
already in the maintenance phase of this study as of 5/11/04 continue to receive erlotinib
once daily for up to 2 years) in the absence of disease progression or unacceptable
In both regimens, cohorts of 3-6 patients receive escalating doses of erlotinib until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed at 30 days and then every 3 months for up to 2 years.
PROJECTED ACCRUAL: A total of 24-48 patients (12-24 per regimen) will be accrued for this
study within 6-24 months.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of cisplatin, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v3.0
Summarized using descriptive statistics.
Up to 7 weeks
Johns Hopkins University
United States: Food and Drug Administration
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