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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00227513
Recruitment Status : Completed
First Posted : September 28, 2005
Last Update Posted : February 24, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE September 26, 2005
First Posted Date  ICMJE September 28, 2005
Last Update Posted Date February 24, 2014
Study Start Date  ICMJE July 2005
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2013)
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2013)
  • Anti-tumor activity by tumor measurements assessed by RECIST [ Time Frame: Up to 5 years ]
  • Peak plasma concentration (Cmax) of SAHA [ Time Frame: Days 1, 2, and 12 ]
  • Time to SAHA Cmax (Tmax) [ Time Frame: Days 1, 2, and 12 ]
  • Clearance of SAHA [ Time Frame: Days 1, 2, and 12 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vorinostat and Bortezomib in Treating Patients With Metastatic or Unresectable Solid Tumors
Official Title  ICMJE A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Bortezomib in Patients With Advanced Malignancies
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unspecified Adult Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Drug: bortezomib
    Given IV
    Other Names:
    • LDP 341
    • MLN341
    • VELCADE
  • Drug: vorinostat
    Given orally
    Other Names:
    • L-001079038
    • SAHA
    • suberoylanilide hydroxamic acid
    • Zolinza
Study Arms  ICMJE 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.

Interventions:
  • Drug: bortezomib
  • Drug: vorinostat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 21, 2009)
66
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00227513
Other Study ID Numbers  ICMJE NCI-2009-00097
NCI-2009-00097 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000441195
H-2005-0205
CO 04906 ( Other Identifier: University of Wisconsin Hospital and Clinics )
6910 ( Other Identifier: CTEP )
P30CA014520 ( U.S. NIH Grant/Contract )
U01CA062491 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: George Wilding University of Wisconsin, Madison
PRS Account National Cancer Institute (NCI)
Verification Date April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP