A Phase 1 Study of Vorinostat in Combination With Paclitaxel and Carboplatin in Solid Tumors (With Focus on Upper Aerodigestive Cancers) in Persons With HIV Infection
I. Determine the safety and tolerability of vorinostat in combination with paclitaxel and
carboplatin in patients with solid tumors and HIV infection.
II. Determine the maximum-tolerated dose (MTD) of this combination in this patient
I. Preliminarily assess response rates to this therapeutic combination in patients with
lung, head and neck, and esophageal cancers.
II. Evaluate the pathological characteristics of non-AIDS-defining cancers of the upper
III. Determine the presence and oncogenic activity of human papillomavirus (HPV) infection
in tumor tissue and to correlate HPV infection with clinical outcomes.
IV. Investigate the effects of vorinostat with chemotherapy on patient immune status, HIV
viral load, and latent viral reservoirs in memory T cells using highly sensitive assays.
V. Investigate possible pharmacokinetic interactions between paclitaxel and antiretroviral
therapy in persons with HIV infection.
VI. Investigate possible pharmacokinetic interactions between ritonavir and vorinostat in
patients with HIV infection.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat followed by an expansion
cohort study. Patients are stratified according to highly active antiretroviral therapy
(HAART) (ritonavir-based HAART vs other or no HAART vs efavirenz-based HAART [expansion
Patients receive oral vorinostat once daily on days 1-5 and paclitaxel IV over 3 hours and
carboplatin IV over 30 minutes on day 3. Treatment repeats every 21 days for up to 6 courses
in the absence of disease progression or unacceptable toxicity.
Some patients undergo blood sample collection at baseline and periodically during course 1
for pharmacokinetic studies and HIV viral load analysis.
After completion of study therapy, patients are followed up every 6 months for up to 3
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose of vorinostat in combination with paclitaxel and carboplatin determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)
AIDS Associated Malignancies Clinical Trials Consortium
United States: Food and Drug Administration
|Montefiore Medical Center||Bronx, New York 10467-2490|
|Pennsylvania Oncology Hematology Associates||Philadelphia, Pennsylvania 19107|
|University of Miami Miller School of Medicine-Sylvester Cancer Center||Miami, Florida 33136|
|AIDS - Associated Malignancies Clinical Trials Consortium||Rockville, Maryland 20850|