PXD101 and Isotretinoin in Treating Patients With Solid Tumors That Are Metastatic or That Cannot Be Removed by Surgery
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Unspecified Adult Solid Tumor, Protocol Specific
Intervention: belinostat (Drug); isotretinoin (Drug); biopsy (Procedure); gene expression analysis (Procedure); gene expression profiling (Procedure); laboratory biomarker analysis (Procedure); pharmacological study (Procedure)
Phase: Phase 1
Status: Recruiting
Sponsored by: California Cancer Consortium Official(s) and/or principal investigator(s):
Thehang H. Luu, MD, Study Chair, Affiliation: Beckman Research Institute
Summary
RATIONALE: PXD101 may stop the growth of tumor cells by blocking blood flow to the tumor and
by blocking some of the enzymes needed for cell growth. Isotretinoin may cause solid tumor
cells to look more like normal cells, and to grow and spread more slowly. Giving PXD101
together with isotretinoin may be an effective treatment for metastatic or unresectable solid
tumors.
PURPOSE: This phase I trial is studying the side effects and best dose of PXD101 when given
together with isotretinoin in treating patients with metastatic or unresectable solid
tumors.
Clinical Details
Official title: A Phase I Trial of PXD101 in Combination With 13-Cis-Retinoic Acid in Advanced Solid Tumor Malignancies
Study design: Treatment
Detailed description:
OBJECTIVES:
Primary
- Determine the safety and tolerability of PXD101 when administered with isotretinoin in
patients with metastatic or unresectable solid tumors.
- Determine the maximum tolerated dose of PXD101 when administered with isotretinoin in
these patients.
- Determine the toxic effects of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
Secondary
- Demonstrate upregulation of retinoic acid receptor-beta and retinoic X-receptor
expression in tumor tissue from patients treated with this regimen.
- Correlate apoptosis in tumor tissue with tumor response in patients treated with this
regimen.
- Determine the change in gene expression after exposure to this regimen.
- Determine any clinical activity of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of PXD101.
Patients receive PXD101 IV over 30 minutes on days 1-5 and oral isotretinoin once daily 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
pharmacokinetic studies.
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.
PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed solid tumor
- Metastatic or unresectable disease
- Refractory to standard curative or palliative treatments or these treatments do not
exist
- No known brain metastases
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100%
- Life expectancy > 3 months
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin normal
- AST and ALT ≤ 2. 5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception prior to, during, and for 30 days
after completion of study treatment
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to PXD101
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No marked baseline prolongation of QT/QTc interval (e. g., repeated demonstration of a
QTc interval > 500 msec)
- No long QT syndrome
- No significant cardiovascular disease, including any of the following:
- Unstable angina pectoris
- Uncontrolled hypertension
- Congestive heart failure related to primary cardiac disease
- Any condition requiring anti-arrhythmic therapy
- Ischemic or severe valvular heart disease
- Myocardial infarction within the past 6 months
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy and recovered
- At least 2 weeks since prior valproic acid
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies
- No concurrent medication that may cause torsades de pointes, including any of the
following:
- Disopyramide
- Dofetilide
- Ibutilide
- Procainamide
- Quinidine
- Sotalol
- Bepridil
- Amiodarone
- Arsenic trioxide
- Cisapride
- Lidoflazine
- Clarithromycin
- Erythromycin
- Halofantrine
- Pentamidine
- Sparfloxacin
- Domperidone
- Droperidol
- Chlorpromazine
- Haloperidol
- Mesoridazine
- Thioridazine
- Pimozide
- Methadone
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No prophylactic filgrastim (G-CSF) during the first course of study treatment
Locations and Contacts
City of Hope Comprehensive Cancer Center, Duarte, California 91010-3000, United States; Recruiting
Clinical Trials Office - City of Hope Comprehensive Cancer Cen, Phone: 800-826-4673, Email: becomingapatient@coh.org
Contra Costa Regional Medical Center, Martinez, California 94553, United States; Recruiting
Sharon Hiner, MD, Phone: 925-370-5114, Email: shiner@hsd.co.contra-costa.ca.us
University of California Davis Cancer Center, Sacramento, California 95817, United States; Recruiting
Clinical Trials Office - University of California Davis Cancer, Phone: 916-734-3089
USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles, California 90089-9181, United States; Recruiting
Clinical Trials Office - USC/Norris Comprehensive Cancer Cente, Phone: 323-865-0451
UPMC Cancer Centers, Pittsburgh, Pennsylvania 15232, United States; Recruiting
Clinical Trials Office - UPMC Cancer Centers, Phone: 412-647-8073
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: June 2006
Last updated: July 23, 2008
|
