Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	PCI-PHI-51 PCI-UPC-04-170, PCI-0504020, NCI-6922, 6922, NCT00287937

Objectives

Primary

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

Secondary

1. Determine the dose-limiting toxicity (DLT) and other toxic effects of this regimen in these patients.
2. Assess, preliminarily, evidence of antitumor activity of this regimen in these patients.
3. Determine the pharmacokinetic parameters of this regimen in these patients.
4. Determine the in vivo effects of this regimen in these patients.

Entry 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

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

Patient Characteristics:

• ECOG performance status ≤ 2 OR Karnofsky performance status 60-100%
• Life expectancy > 12 weeks
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

A total of 30 patients will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

UPMC Cancer Centers

Suresh Ramalingam, MD, Protocol chair		Ph: 412-648-6619 Email: sar18@pitt.edu

Registry Information
Official Title		Phase I Study Of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) in Combination With Paclitaxel /Carboplatin for Advanced and Refractory Solid Malignancies
Trial Start Date		2005-07-28
Registered in ClinicalTrials.gov		NCT00287937
Date Submitted to PDQ		2005-09-16
Information Last Verified		2006-03-23
NCI Grant/Contract Number		CA47904, CA99168, CA62505

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