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A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Bortezomib in Patients With Advanced Malignancies


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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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 ClinicsMadison, Wisconsin  53792-0001