Clinical trial NCT00287937: Vorinostat, Paclitaxel, and Carboplatin in Treating Patients With Advanced or Refractory Solid Tumors
Official title: Phase I Study Of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) in Combination With Paclitaxel /Carboplatin for Advanced and Refractory Solid Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-02-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: MTD of vorinostat defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT
timeFrame: 21 days
Secondary outcomes:
measure: Toxicity graded using the CTC version 2.0
timeFrame: Up to 1 month after completion of study treatment
measure: Overall survival
timeFrame: Up to 1 month after completion of study treatment
measure: Time to failure
timeFrame: Up to 1 month after completion of study treatment
measure: Response defined using the RECIST criteria
timeFrame: Up to 1 month after completion of study treatment
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Suresh Ramalingam
role: PRINCIPAL_INVESTIGATOR
References: