Study of Oral PXD101 in Patients With Advanced Solid Tumors or Lymphoma

This is a Phase I dose escalation study of PXD101 administered orally. Oral belinostat will be given once or twice daily at various dosing schedules to patients with solid tumors. Doses will be escalated until the maximum tolerated dose (MTD) is identified. In parallel, a cohort of lymphoma patients will be given oral belinostat on a discontinuous once daily dosing schedule...

Date First Received: December 18, 2006

Last Updated: January 29, 2008

Verified by: CuraGen Corporation, January 2008

Clinical Trial Phase: Phase 1 Start Date: July 2006

Overall Status: Recruiting

Estimated Enrollment: 100

Brief Summary

Official Title: “Open Label, Dose Escalation Trial of Oral PXD101 in Patients With Advanced Solid Tumors”

Condition Keyword(s):

• Solid Tumor


• Lymphoma

Intervention(s):

• Drug: belinostat

This is a Phase I dose escalation study of PXD101 administered orally. Oral belinostat will be given once or twice daily at various dosing schedules to patients with solid tumors. Doses will be escalated until the maximum tolerated dose (MTD) is identified. In parallel, a cohort of lymphoma patients will be given oral belinostat on a discontinuous once daily dosing schedule.

Study Type: Interventional

Study Design: Treatment, Open Label, Single Group Assignment, Safety Study

Outcome Measures for this Clinical Trial

Primary:

• Safety, tolerability and maximum tolerated dose of orally administered PXD101 for each cohort throughout the study

Secondary:

• Determine the pharmacokinetics of oral PXD101 when dosed once or twice daily at various dose levels throughout the study


• Explore anti-tumor activity throughout the study


• Determine the safety, tolerability, and anti-tumor activity of orally administered PXD101 to patients with lymphoma throughout the trial

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Age ≥ 18 years


• Solid tumor: Histologically confirmed solid tumors.


• Lymphoma: relapsed or refractory B-cell or T-cell lymphoma or Hodgkins disease


• At least one evaluable lesion. Lesions must be evaluated by computed tomography (CT), magnetic resonance imaging (MRI), or bone scan. Patients with prostate cancer, bone disease and rising prostate-specific antigen [PSA] but no other evaluable disease are eligible and will be evaluated based on PSA.


• Progressive disease: Progressive disease will be defined as new or progressive lesions on CT-scan, MRI, bone scan or by rising PSA


• ≥ 4 weeks since prior radiation therapy or chemotherapy


• Karnofsky performance ≥ 60%


• Acceptable liver, renal and bone marrow function to include:


• absolute neutrophil count ≥ 1.5 x 10^9/L


• hemoglobin ≥ 9.0 g/dl


• platelets ≥ 100 x 10^9/L


• bilirubin ≤ 1.5 x upper limit of normal (ULN)


• AST and ALT ≤ 3.0 x ULN (≤ 5.0 x ULN is acceptable if liver has tumor involvement)


• serum creatinine ≤ 1.5 x ULN


• PT-INR/PTT ≤ 1.5 x ULN, or for patients on anticoagulation therapy, status within therapeutic range


• Serum potassium within normal range


• Estimated life expectancy of greater than 3 months


• Signed informed consent prior to any study specific procedures

Exclusion Criteria:

• Prior treatment with PXD101


• Within 4 weeks of enrollment:


• major surgery


• metastatic disease requiring palliative treatment


• Anticancer therapy, including:


• chemotherapy


• radiotherapy


• endocrine therapy


• immunotherapy


• other investigational agents (6 weeks for mitomycin or nitrosourea)


• Serious concomitant systemic disorders (eg, active infection) compromising patient safety.


• Symptomatic brain metastases


• Significant cardiovascular disease, including:


• unstable angina pectoris


• uncontrolled hypertension


• congestive heart failure (New York Heart Association [NYHA] Class III or IV) related to primary cardiac disease, a condition requiring anti-arrhythmic therapy


• ischemic or severe valvular heart disease


• myocardial infarction within 6 months prior to the trial entry


• A marked baseline prolongation of QT/QTc interval, such as:


• repeated demonstration of a QTc interval > 500 msec


• Long QT syndrome


• required use of concomitant medication on dosing days that may cause torsade de pointes


• Altered mental status precluding understanding of the informed consent process and/or completion of the study


• Pregnant or breast-feeding women


• Refusal or inability to use effective means of contraception (for men and women of childbearing potential)


• History of, or test positive for, HIV.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: CuraGen Corporation

Yale New Haven Hospital

New Haven Connecticut 06520 United States

Columbia University - Herbert Irving Cancer Center

New York New York 01132 United States

M.D. Anderson Cancer Center

Houston Texas 77230-1402 United States

Research Facility

Copenhagen Denmark

Research Facility

London Surrey SW3 6JJ United Kingdom

Overall Clinical Trial Officials and Contacts

Overall Contact: CuraGen Clinical Trial Call Center
877-462-4363
info@curagen.com

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00413075

Study ID Number: PXD101-CLN-9

ClinicalTrials.gov Identifier: NCT00413075

Health Authority: United States: Food and Drug Administration

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Labels: ClinicalTrial