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
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Objective tumor response (complete and partial overall response) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
Overview
Brief Summary
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
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed adenoid cystic carcinoma of the head and neck
- •Locally advanced, recurrent, or metastatic disease that is considered incurable by known therapies
- •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
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (bortezomib, doxorubicin hydrochloride)
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.
Intervention: bortezomib (Drug)
Treatment (bortezomib, doxorubicin hydrochloride)
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.
Intervention: doxorubicin hydrochloride (Drug)
Treatment (bortezomib, doxorubicin hydrochloride)
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.
Intervention: laboratory biomarker analysis (Other)
Outcomes
Primary Outcomes
Objective tumor response (complete and partial overall response) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Up to 10 years
Secondary Outcomes
- Toxicities, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0(Up to 30 days after last dose of study treatment)
- Progression free survival(Time from randomization or registration to the earlier of disease recurrence or death from any cause, assessed up to 10 years)
- Overall survival(Time from randomization or registration to date of death (from any cause) or date of last contact, assessed up to 10 years)
- Association of change in cytokine concentration with response to bortezomib therapy(Up to 1 hour post-treatment (course 2))
- Correlation of the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway on tumor tissue with clinical activity(Baseline)