Vorinostat and Bortezomib in Treating Patients With Metastatic or Unresectable Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00227513
First received: September 26, 2005
Last updated: February 21, 2014
Last verified: April 2013
  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. 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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: bortezomib
Drug: vorinostat
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Bortezomib in Patients With Advanced Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Frequency and severity of toxicity incidents assessed by Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Anti-tumor activity by tumor measurements assessed by RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Peak plasma concentration (Cmax) of SAHA [ Time Frame: Days 1, 2, and 12 ] [ Designated as safety issue: No ]
  • Time to SAHA Cmax (Tmax) [ Time Frame: Days 1, 2, and 12 ] [ Designated as safety issue: No ]
  • Clearance of SAHA [ Time Frame: Days 1, 2, and 12 ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: July 2005
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

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.

Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: vorinostat
Given orally
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza

Detailed Description:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: George Wilding University of Wisconsin Hospital and Clinics
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00227513     History of Changes
Other Study ID Numbers: NCI-2009-00097, NCI-2009-00097, CDR0000441195, H-2005-0205, CO 04906, 6910, P30CA014520, U01CA062491
Study First Received: September 26, 2005
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bortezomib
Vorinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014