PXD101 and Isotretinoin in Treating Patients With Solid Tumors That Are Metastatic or That Cannot Be Removed by Surgery - Full Text View

Sponsor:	California Cancer Consortium
Collaborator:	National Cancer Institute (NCI)
Information provided by:	California Cancer Consortium
ClinicalTrials.gov Identifier:	NCT00334789

Purpose

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.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: belinostat	Phase I

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Trial of PXD101 in Combination With 13-cis-Retinoic Acid in Advanced Solid Tumor Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Belinostat Isotretinoin

U.S. FDA Resources

Further study details as provided by California Cancer Consortium:

Primary Outcome Measures:

1.1.1 To assess the safety and feasibility of combining PXD101 with 13-cis-retinoic acid (13-cRA) in patients with advanced solid tumor malignancies. [ Time Frame: end of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	36
Study Start Date:	June 2006
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Intervention Details:

PXD101 is administered daily dose x 5days as a 30-minute infusion week one every 3 weeks. Infuse PXD 101 intravenously over 30 minutes through an in-line 0.22 micron low protein binding filter

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.

NOTE: * A subset of patients also undergo blood collectiion for pharmacokinetic studies of PXD101, at the highest dose levels even though MTD has not been reached, with or without isotretinoin.

PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00334789

Locations

United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org
USC/Norris Comprehensive Cancer Center and Hospital	Recruiting
Los Angeles, California, United States, 90089-9181
Contact: Clinical Trials Office - USC/Norris Comprehensive Cancer Cente 323-865-0451
Contra Costa Regional Medical Center	Recruiting
Martinez, California, United States, 94553
Contact: Sharon Hiner, MD 925-370-5114 shiner@hsd.co.contra-costa.ca.us
University of California Davis Cancer Center	Recruiting
Sacramento, California, United States, 95817
Contact: Clinical Trials Office - University of California Davis Cancer 916-734-3089
United States, Pennsylvania
UPMC Cancer Centers	Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Clinical Trials Office - UPMC Cancer Centers 412-647-8073

Sponsors and Collaborators

California Cancer Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

Thehang H. Luu, MD

Beckman Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Thehang Lu, California Cancer Consortium
ClinicalTrials.gov Identifier:	NCT00334789 History of Changes
Other Study ID Numbers:	CDR0000479715, U01CA062505, CCC-PHI-53, NCI-7251
Study First Received:	June 7, 2006
Last Updated:	June 14, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by California Cancer Consortium:

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Neoplasms
Isotretinoin
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012