A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Bortezomib in Patients With Advanced Malignancies
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Bortezomib in Patients With Advanced Malignancies
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of vorinostat (SAHA) and bortezomib in patients with
metastatic or unresectable solid tumors.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and antitumor activity of this regimen in these patients.
II. Determine the toxic effects of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oral vorinostat (SAHA) twice daily on days 1-14 in step A. Patients receive
oral vorinostat (SAHA) twice daily on days 1-4 and 8-11 in Step B and bortezomib IV over 3-5
seconds on days 2, 5, 9, and 12 during the first course and on days 1, 4, 8, and 11 during
subsequent courses in both steps A and B. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.
Cohorts of 1-6 patients receive escalating doses of bortezomib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Up to 6 additional patients receive
bortezomib at the MTD. Subsequent cohorts of 3-6 patients receive escalating doses of SAHA
until the MTD of that drug is determined.
Inclusion Criteria:
- Histologically confirmed malignancy, metastatic or unresectable disease
- Standard curative or palliative measures do not exist OR are no longer effective
- Measurable or evaluable disease
- No known brain metastases
- ECOG 0-2 OR Karnofsky 60-100%
- Life expectancy > 12 weeks
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- No history of myocardial infarction
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No severe pulmonary disease requiring oxygen
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 28 days after study
participation
- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to study drugs or agents
- No pre-existing neuropathy ≥ grade 2
- No uncontrolled illness
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered
- No prior radiotherapy to > 25% of bone marrow
- At least 4 weeks since prior radiotherapy and recovered
- At least 2 weeks since prior valproic acid
- No prior bortezomib
- No concurrent enzyme-inducing anticonvulsant agents
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
Outcome Time Frame:
21 days
Safety Issue:
Yes
Principal Investigator
George Wilding
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Wisconsin Hospital and Clinics
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00097
NCT ID:
NCT00227513
Start Date:
July 2005
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
Name | Location |
|---|---|
| University of Wisconsin Hospital and Clinics | Madison, Wisconsin 53792-0001 |
