Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Treatment	Active	18 and over	NCI	CCC-PHI-53 7251, NCI-7251, NCT00334789

Objectives

Primary

1. Determine the safety and tolerability of PXD101 when administered with isotretinoin in patients with metastatic or unresectable solid tumors.
2. Determine the maximum tolerated dose of PXD101 when administered with isotretinoin in these patients.
3. Determine the toxic effects of this regimen in these patients.
4. Determine the pharmacokinetics of this regimen in these patients.

Secondary

1. Demonstrate upregulation of retinoic acid receptor-beta and retinoic X-receptor expression in tumor tissue from patients treated with this regimen.
2. Correlate apoptosis in tumor tissue with tumor response in patients treated with this regimen.
3. Determine the change in gene expression after exposure to this regimen.
4. Determine any clinical activity of this regimen in these patients.

Entry 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

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

Patient Characteristics:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

California Cancer Consortium

Thehang Luu, MD, Protocol chair		Ph: 626-359-8111 ext. 62307; 800-826-4673 Email: tluu@coh.org

U.S.A.
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Martinez
	Contra Costa Regional Medical Center
		Sharon Hiner, MD	Ph:  925-370-5114 800-232-4636
			Email: shiner@hsd.co.contra-costa.ca.us
	Sacramento
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
Pennsylvania
	Pittsburgh
	UPMC Cancer Centers
		Clinical Trials Office - UPMC Cancer Centers	Ph:  412-647-8073

Registry Information
Official Title		A Phase I Trial of PXD101 in Combination with 13-cis-Retinoic Acid in Advanced Solid Tumor Malignancies
Trial Start Date		2006-06-12
Trial Completion Date		2007-05-18 (estimated)
Registered in ClinicalTrials.gov		NCT00334789
Date Submitted to PDQ		2006-04-03
Information Last Verified		2009-06-07
NCI Grant/Contract Number		CA62505

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