A Phase 1 Trial of PXD101 in Combination With 13-cis-Retinoic Acid in Advanced Solid Tumor Malignancies
I. To assess the safety and feasibility of combining PXD101 (belinostat) with
13-cis-retinoic acid [13-cRA] (isotretinoin) in patients with advanced solid tumor
II. To define the maximum tolerated dose (MTD) of PXD101 when administered in combination
with 13-cRA and to describe the toxicities at each dose studied.
III. To evaluate the pharmacokinetics of PXD101 and 13-cRA when given in combination.
I. To demonstrate upregulation of retinoic acid receptor-beta (RARβ) and retinoic X-receptor
(RXR) expression in tumor tissues after treatment with PXD101 and 13-cRA.
II. To measure apoptosis in tumor biopsies after treatment. III. To assess the change in
gene expression after exposure to PXD101 and 13-cRA.
IV. To document any clinical activity of the combination of PXD101 and 13-cRA.
OUTLINE: This is a multicenter, dose-escalation study of belinostat.
Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5 and isotretinoin
orally (PO) once daily (QD) on days 1-14. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of PXD101 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 dose-limiting toxicity during the first course of therapy.
Once the MTD is determined, an expanded cohort of 10 patients are enrolled and treated at
the MTD. These patients also undergo blood collection periodically during treatment for
All patients undergo blood collection, buccal scrapings, and tumor biopsies periodically for
biomarker, pharmacodynamic, gene expression, and laboratory studies.
After completion of study treatment, patients are followed for >= 8 weeks.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of belinostat in combination with isotretinoin determined by dose limiting toxicities graded according to NCI CTCAE 4.0
Tables will be created to summarize these toxicities and side effects by dose and by cycle. Tabular and graphical summaries will be used to explore the relationship of type and grade of toxicity to dose, cycle, and pharmacokinetics.
Beckman Research Institute
United States: Food and Drug Administration
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|
|City of Hope Medical Center||Duarte, California 91010|
|City of Hope||Duarte, California 91010|
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|University of Southern California||Los Angeles, California 90033|