Vorinostat and Bortezomib in Treating Patients With Metastatic or Unresectable Solid Tumors - Full Text View

Sponsors and Collaborators:	University of Wisconsin, Madison National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00227513

Purpose

RATIONALE: Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with bortezomib may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat and bortezomib in treating patients with metastatic or unresectable solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: bortezomib Drug: vorinostat	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Suberoylanilide hydroxamic acid Bortezomib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Bortezomib in Patients With Advanced Malignancies

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose at course 1 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics at course 1 and 2 [ Designated as safety issue: No ]
Anti-tumor activity by tumor measurements using the RECIST criteria at courses 1 and 2 [ Designated as safety issue: No ]
Toxicity at course 1 and 2 [ Designated as safety issue: Yes ]

Estimated Enrollment:	36
Study Start Date:	July 2005
Estimated Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of vorinostat (SAHA) and bortezomib in patients with metastatic or unresectable solid tumors.

Secondary

Determine the pharmacokinetics and antitumor activity of this regimen in these patients.
Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral vorinostat (SAHA) once 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.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 14 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy

More than 12 weeks

Hematopoietic

WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal

Renal

Creatinine normal OR
Creatinine clearance ≥ 60 mL/min

Cardiovascular

No history of myocardial infarction
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Pulmonary

No severe pulmonary disease requiring oxygen

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy to > 25% of bone marrow
At least 4 weeks since prior radiotherapy and recovered

Surgery

Not specified

Other

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00227513

Locations

United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Recruiting
Madison, Wisconsin, United States, 53792-6164
Contact: Clinical Trials Office - University of Wisconsin Paul P. Carbo 608-262-5223

Sponsors and Collaborators

University of Wisconsin, Madison

National Cancer Institute (NCI)

Investigators

Principal Investigator:

George Wilding, MD

University of Wisconsin, Madison

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000441195, WCCC-CO-04906, NCI-6910
Study First Received:	September 26, 2005
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00227513
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Bortezomib
Vorinostat

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions
Protease Inhibitors

Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009