Vorinostat and Carboplatin or Vorinostat and Paclitaxel in Patients With Advanced Solid Tumors: A Pharmacokinetic and Pharmacodynamic Study
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Vorinostat and Carboplatin or Vorinostat and Paclitaxel in Patients With Advanced Solid Tumors: A Pharmacokinetic and Pharmacodynamic Study
PRIMARY OBJECTIVES:
I. To determine whether high dose, short course vorinostat achieves higher peak serum
concentrations than standard dosing.
SECONDARY OBJECTIVES:
I. To determine the toxicity profiles of two different escalated intermittent dosing
schedules of vorinostat combined with carboplatin at an area under curve (AUC) of 5.
II. To describe the response rate in patients with advanced solid tumors treated with these
regimens.
III. To develop pharmacodynamic markers for vorinostat. IV. To determine the toxicity
profiles of escalated intermittent dosing schedule of vorinostat at 1200 mg combined with
paclitaxel at 175 mg/m^2 and to describe the response rate in patients with advanced solid
tumors treated with this regimen.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive high-dose vorinostat orally (PO) once daily (QD) on days 1-3 and
low-dose vorinostat PO QD on days 8-10 (course 1). After 5 days, patients receive high-dose
vorinostat PO QD on days 1-3 and carboplatin IV over 30 minutes on day 3 of all subsequent
courses.
ARM II: Patients receive high-dose vorinostat and low-dose vorinostat as in arm I. After 5
days, patients receive lower-dose vorinostat PO QD on days 1-3 and carboplatin IV over 30
minutes on day 3 of all subsequent courses.
ARM III: Patients receive low-dose vorinostat PO QD on days 1-3 and high-dose vorinostat PO
QD on days 8-10 (course 0). After 5 days, patients receive vorinostat and carboplatin as in
arm I.
ARM IV: Patients receive low-dose vorinostat and high-dose vorinostat as in arm III. After 5
days, patients receive vorinostat and carboplatin as in arm II.
ARM V: Patients receive low-dose vorinostat PO QD on days 1-3 and mid-dose vorinostat PO QD
on days 8-10 (course 0). After 5 days, patients receive mid-dose vorinostat PO QD on days
1-3 and paclitaxel IV over 3 hours on day 3.
ARM VI: Patients receive mid-dose vorinostat PO QD on days 1-3 and low-dose vorinostat PO QD
on days 8-10 (course 0). After 5 days, patients receive vorinostat and paclitaxel as in arm
V.
In all arms, courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.
After completion of study therapy, patients are followed up for 4 weeks.
Inclusion Criteria:
- Histologically confirmed malignancy that is metastatic or unresectable and for which
no superior curative or palliative measures are known
- No known brain metastases that are untreated or have progressed after definitive
therapy
- Patients with treated brain metastases who are no longer receiving steroids (for
at least 14 days) or enzyme-inducing anti-epileptic drugs and who have no
unstable neurologic symptoms may be enrolled at the discretion and joint
decision of the principal investigator and treating physician
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Life expectancy > 3 months
- Leukocytes > 3,000/mm³
- Absolute neutrophil count > 1,500/mm^3
- Platelet count > 100,000/mm^3
- Total bilirubin normal
- Potassium normal
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 times upper
limit of normal (ULN) (< 5 times ULN for patients with liver metastases)
- Creatinine normal OR creatinine clearance > 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Women of child-bearing potential and men must agree to use adequate contraception for
the duration of the study
- Able to swallow oral medications
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to vorinostat or carboplatin
- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- At least 4 weeks since prior chemotherapy or radiotherapy (6 weeks for carmustine
[BCNU], nitrosoureas, or mitomycin C) and recovered to grade ≤ 1 toxicity
- No prior or concurrent valproic acid
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for human immunodeficiency virus
(HIV)-positive patients
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Peak concentrations (Cmax) of vorinostat at 400, 1200, and 1600 mg
Outcome Time Frame:
0 (pre-treatment), 60, 120, 180, 240, 360 and 480 minutes and 24 hours after vorinostat administration on days 3 and 10 of course 0 and on day 3 of course 1
Safety Issue:
No
Principal Investigator
Michael Maitland
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Chicago Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2011-02575
NCT ID:
NCT01281176
Start Date:
February 2011
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
