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

NCT ID: NCT00287937

Last Updated: 2013-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31

Brief Summary

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

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

Given orally

paclitaxel

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

vorinostat

Given orally

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

carboplatin

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; Anzatax; Asotax; TAX; Taxol; Carboplat; CBDCA; JM-8; Paraplat; Paraplatin; pharmacological studies

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suresh Ramalingam

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

PHI 51

Identifier Type: -

Identifier Source: secondary_id

U01CA099168

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062505

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000454713

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02676

Identifier Type: -

Identifier Source: org_study_id