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Vorinostat, Paclitaxel, and Carboplatin in Treating Patients With Advanced or Refractory Solid Tumors

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00287937
First Posted: February 7, 2006
Last Update Posted: February 7, 2013
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.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This phase I trial is studying the side effects and best dose of vorinostat when given together with paclitaxel and carboplatin in treating patients with advanced or refractory solid tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with paclitaxel and carboplatin may kill more tumor cells

Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: vorinostat Drug: paclitaxel Drug: carboplatin Other: laboratory biomarker analysis Other: pharmacological study Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study Of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) in Combination With Paclitaxel /Carboplatin for Advanced and Refractory Solid Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MTD of vorinostat defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT [ Time Frame: 21 days ]

Secondary Outcome Measures:
  • Toxicity graded using the CTC version 2.0 [ Time Frame: Up to 1 month after completion of study treatment ]
    Tables will be created to summarize these toxicities by dose and by course.

  • Overall survival [ Time Frame: Up to 1 month after completion of study treatment ]
    Summarized with Kaplan-Meier plots.

  • Time to failure [ Time Frame: Up to 1 month after completion of study treatment ]
    Summarized with Kaplan-Meier plots.

  • Response defined using the RECIST criteria [ Time Frame: Up to 1 month after completion of study treatment ]

Enrollment: 30
Study Start Date: July 2005
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vorinostat, paclitaxel, carboplatin)
Patients receive oral SAHA once or twice daily on days 1-14* and paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease after the completion of 6 courses may receive single-agent SAHA at the discretion of the treating physician.
Drug: vorinostat
Given orally
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the recommended phase II dose of vorinostat (SAHA) when administered with paclitaxel and carboplatin in patients with advanced or refractory solid tumors.

SECONDARY OBJECTIVES:

I. Determine the dose-limiting toxicity (DLT) and other toxic effects of this regimen in these patients.

II. Assess, preliminarily, evidence of antitumor activity of this regimen in these patients.

III. Determine the pharmacokinetic parameters of this regimen in these patients.

IV. Determine the in vivo effects of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA).

Patients receive oral SAHA once or twice daily on days 1-14* and paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease after the completion of 6 courses may receive single-agent SAHA at the discretion of the treating physician.

NOTE: *During the first treatment course only, patients receive SAHA on days -4 to 10.Cohorts of 3-6 patients receive escalating doses of SAHA 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 DLT. An additional 6-12 patients are treated at the MTD.

After completion of study treatment, patients are followed at 1 month.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed solid tumor
  • No untreated brain metastases

    • Patients with stable brain disease (no concurrent corticosteroids) ≥ 4 weeks after completion of appropriate therapy are eligible
  • ECOG performance status ≤ 2 OR Karnofsky performance status 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/ALT ≤ 2.5 times upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double barrier contraception for at least 1 week before, during, and for at least 2 weeks after study participation
  • No peripheral neuropathy > grade 1
  • No history of allergic reactions to paclitaxel
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
  • No inability to take oral medications on a continuous basis
  • No psychiatric illness or social situation that would limit compliance with this study
  • No ongoing or active infection
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No other uncontrolled illness
  • No more than 2 prior chemotherapy regimens for advanced/metastatic disease

    • Adjuvant chemotherapy administered ≥ 2 years prior to study entry is not considered a prior chemotherapy regimen for purposes of this study
  • No prior therapy with paclitaxel
  • No chemotherapy or radiotherapy within the past 3 weeks (6 weeks for nitrosoureas or mitomycin C) and recovered
  • At least 4 weeks since prior valproic acid
  • No other concurrent anticancer therapies or agents
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent oral contraceptives
  • No concurrent prophylactic growth factors
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00287937


Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Suresh Ramalingam University of Pittsburgh
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00287937     History of Changes
Other Study ID Numbers: NCI-2012-02676
PHI 51
U01CA099168 ( U.S. NIH Grant/Contract )
U01CA062505 ( U.S. NIH Grant/Contract )
CDR0000454713 ( Registry Identifier: PDQ (Physician Data Query) )
First Submitted: February 6, 2006
First Posted: February 7, 2006
Last Update Posted: February 7, 2013
Last Verified: February 2013

Additional relevant MeSH terms:
Paclitaxel
Vorinostat
Albumin-Bound Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Histone Deacetylase Inhibitors
Enzyme Inhibitors