Phase I Study of Bortezomib and Cetuximab Without or With Cisplatin in Combination With Radiation Therapy for Advanced Head and Neck Cancer
- To evaluate the feasibility and toxicity of bortezomib, cetuximab, and radiotherapy
with or without cisplatin in patients with stage IV squamous cell carcinoma of the head
- To identify the maximum tolerated dose of bortezomib for further clinical phase II
- To evaluate the objective response rate, progression-free survival, and overall
survival of patients treated with these regimens.
- To determine the effects of bortezomib and cetuximab with or without cisplatin on
inhibiting activation of the NF-kB, EGFR, MAPK, and STAT3 signal pathways, expression
of pro-survival and pro-angiogenesis genes regulated by these pathways, and on
proliferation, apoptosis, and angiogenesis.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Patients are
simultaneously accrued to 1 of 2 treatment groups. Patients are initially accrued to group I
until there are a sufficient number of patients to establish the maximum tolerated dose
(MTD) of bortezomib. Patients are then accrued to group II.
- Group I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43,
and 50. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, 11, 22,
25, 29, 32, 43, 46, 50, and 53. Beginning on day 8 or 9, patients undergo standard
intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for up to 8 weeks.
Once the MTD of bortezomib is determined, at least 6 and up to 10 additional patients are
accrued and treated at the MTD.
- Group II: Patients receive cetuximab, bortezomib (beginning at one dose level below the
MTD determined in group I), and IMRT as in group I. Patients also receive cisplatin IV
over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.
Once the MTD of bortezomib is determined, 6 additional patients are accrued and treated at
Patients undergo blood sample collection periodically for correlative laboratory studies.
Samples are analyzed for biomarkers by immunohistochemistry, quantitative reverse
transcriptase-polymerase chain reaction, and ELISA.
After completion of study therapy, patients are followed periodically for 2-5 years.
Primary Purpose: Treatment
Dose-limiting toxicities and other toxicities as assessed by NCI CTCAE v3.0
Carter Van Waes, MD, PhD
National Institute on Deafness and Other Communication Disorders (NIDCD)
United States: Food and Drug Administration
|UPMC Cancer Centers||Pittsburgh, Pennsylvania 15232|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|