Phase II Trial of PS-341 (NSC 681239) Followed by the Addition of Doxorubicin at Progression in Advanced Adenoid Cystic Carcinoma of the Head and Neck
OBJECTIVES: Primary I. Determine the objective tumor response in patients with locally
advanced, recurrent, or metastatic adenoid cystic carcinoma of the head and neck treated
Secondary I. Determine the time to progression in patients treated with this drug. II.
Determine the overall survival of patients treated with this drug. III. Determine the toxic
effects of this drug in these patients. IV. Determine the objective tumor response, time to
progression, and overall survival of patients who progress on single-agent bortezomib and
are then treated with doxorubicin and bortezomib.
V. Determine the toxic effects of this regimen in these patients. VI. Determine the profile
and concentration of inflammatory and angiogenic cytokines in serum of patients before and
in response to this regimen.
VII. Correlate the expression of biomarkers which may be affected by the
ubiquitin-proteasome degradation pathway (NF-kB, p53, p27, cyclin D1, cyclin E, vascular
endothelial growth factor [VEGF], MVD, V-CAM, and N-CAM) on tumor tissue with the clinical
activity of bortezomib in these patients.
OUTLINE: This is a multicenter study.
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat
every 21 days in the absence of disease progression or unacceptable toxicity. Patients with
disease progression continue to receive bortezomib as above and doxorubicin IV over 2-5
minutes on days 1 and 8. Treatment repeats every 21 days for up to 14 courses in the absence
of further disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years and then every 6 months for 8 years.
PROJECTED ACCRUAL: A total of 23-37 patients will be accrued for this study within 2.3
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective tumor response (complete and partial overall response) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
Up to 10 years
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
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