Vorinostat, Paclitaxel, and Carboplatin in Treating Patients With Advanced or Refractory Solid Tumors
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on March 21, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Unspecified Adult Solid Tumor, Protocol Specific
Intervention: carboplatin (Drug); paclitaxel (Drug); vorinostat (Drug); chemotherapy (Procedure); enzyme inhibitor therapy (Procedure)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: UPMC Cancer Centers Official(s) and/or principal investigator(s):
Suresh Ramalingam, MD, Study Chair, Affiliation: UPMC Cancer Centers
Summary
RATIONALE: 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.
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.
Clinical Details
Official title: Phase I Study Of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) in Combination With Paclitaxel /Carboplatin for Advanced and Refractory Solid Malignancies
Study design: Treatment
Detailed description:
OBJECTIVES:
Primary
- Determine the recommended phase II dose of vorinostat (SAHA) when administered with
paclitaxel and carboplatin in patients with advanced or refractory solid tumors.
Secondary
- Determine the dose-limiting toxicity (DLT) and other toxic effects of this regimen in
these patients.
- Assess, preliminarily, evidence of antitumor activity of this regimen in these
patients.
- Determine the pharmacokinetic parameters of this regimen in these patients.
- 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.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
- 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
PRIOR CONCURRENT THERAPY:
- 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
Locations and Contacts
Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: July 2005
Last updated: November 14, 2007
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