Phase I Study of Intraarterial ONYX-015 in Combination With Intravenous Cisplatin and Fluorouracil in Patients With Advanced Squamous Cell Cancer of the Head and Neck
I. Determine the feasibility and maximum tolerated dose (MTD) of intraarterial ONYX-015 in
patients with advanced squamous cell cancer of the head and neck.
II. Determine the feasibility and tolerability of intraarterial ONYX-015 at the MTD OR
maximum theraputic dose, whichever is lower, in combination with intravenous cisplatin and
fluorouracil in these patients.
III. Determine the qualitative distribution of ONYX-015 within a limited tumor biopsy and a
normal mucosal biopsy at different dose levels.
IV. Determine the response of these patients to intraarterial ONYX-015. V. Determine the
response of these patients to cisplatin and fluorouracil following intraarterial ONYX-015.
PROTOCOL OUTLINE: This is a dose escalation study. Patients receive intraarterial infusions
of ONYX-015. Treatment repeats once in 3-4 weeks in the absence of disease progression or
Cohorts of 3-8 patients receive escalating doses of ONYX-015 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 5
patients experience dose limiting toxicity.
Patients in cohorts 1-4 are followed for 5 days after infusion, weekly for 3 weeks, at week
6, and monthly thereafter for 4 months.
A fifth or final cohort of 10 patients will receive ONYX-015 at the MTD. If the MTD was not
determined in cohorts 1-4, patients receive the highest dose administered to cohort 4.
Beginning 1-2 days after ONYX-015 infusion, patients receive cisplatin IV over 30-60 minutes
once and fluorouracil IV continuously over 4 days. Treatment repeats in 4 weeks in the
absence of disease progression or unacceptable toxicity. Cisplatin and fluorouracil IV
treatment continues every 3-4 weeks at the discretion of the treating oncologist.
Patients in cohort 5 are followed for 5 days after initial infusion, weekly for 4 weeks, at
week 8, and monthly thereafter for 4 months.
A total of 23-28 patients will be accrued for this study.
Primary Purpose: Treatment
Marshall R. Posner
Dana-Farber Cancer Institute
United States: Federal Government
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|