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Phase I Study Of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) in Combination With Paclitaxel /Carboplatin for Advanced and Refractory Solid Malignancies


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Study Of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) in Combination With Paclitaxel /Carboplatin for Advanced and Refractory Solid Malignancies


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of vorinostat defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Suresh Ramalingam

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02676

NCT ID:

NCT00287937

Start Date:

July 2005

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific

Name

Location

University of PittsburghPittsburgh, Pennsylvania  15261