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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00287937
First received: February 6, 2006
Last updated: February 6, 2013
Last verified: February 2013
  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: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity graded using the CTC version 2.0 [ Time Frame: Up to 1 month after completion of study treatment ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    Summarized with Kaplan-Meier plots.

  • Time to failure [ Time Frame: Up to 1 month after completion of study treatment ] [ Designated as safety issue: No ]
    Summarized with Kaplan-Meier plots.

  • Response defined using the RECIST criteria [ Time Frame: Up to 1 month after completion of study treatment ] [ Designated as safety issue: No ]

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT00287937

Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Investigators
Principal Investigator: Suresh Ramalingam University of Pittsburgh
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00287937     History of Changes
Other Study ID Numbers: NCI-2012-02676, PHI 51, U01CA099168, U01CA062505, CDR0000454713
Study First Received: February 6, 2006
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Vorinostat
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Histone Deacetylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014