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
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
This phase II trial is studying how well bortezomib followed by doxorubicin at the time of disease progression works in treating patients with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (cancer) of the head and neck. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with doxorubicin may kill more tumor cells
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 with bortezomib.
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 years.
Inclusion Criteria:
Histologically confirmed adenoid cystic carcinoma of the head and neck
Unidimensionally measurable disease
Must not have stable disease for at least 9 months before study entry
No known brain metastases
Performance status - ECOG 0-2
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
AST and ALT no greater than 2.5 times upper limit of normal
Bilirubin normal
Creatinine normal
Creatinine clearance at least 60 mL/min
LVEF at least lower limit of normal by MUGA
No history of congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No active or ongoing infection
No prior allergy to compounds of similar chemical or biological composition to bortezomib
No other concurrent uncontrolled illness
No psychiatric illness or social situation that would preclude study compliance
No pre-existing neuropathy > grade 1
No other invasive malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
See Chemotherapy
No prior anthracyclines, including any of the following:
No prior mitoxantrone
No prior high-dose chemotherapy for bone marrow transplantation
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
At least 3 weeks since prior radiotherapy
At least 3 weeks since prior surgery
More than 4 weeks since prior investigational drugs
No other concurrent anticancer therapy or agents