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

Sponsor

Onxeo (Industry)

Overall Status

Completed

CT.gov ID

NCT00413075

Collaborator

Spectrum Pharmaceuticals, Inc (Industry)

121

Enrollment

Locations

Arm

Duration (Months)

20.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Lymphoma	Drug: oral belinostat	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

121 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open Label, Dose Escalation Trial of Oral PXD101 in Patients With Advanced Solid Tumors

Study Start Date :

Jun 1, 2006

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: oral belinostat	Drug: oral belinostat oral belinostat dosed once or twice daily at continuous and discontinuous dosing schedules. Other Names: PXD101

Arm

Intervention/Treatment

Experimental: oral belinostat

Drug: oral belinostat

oral belinostat dosed once or twice daily at continuous and discontinuous dosing schedules.

Other Names:

PXD101

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria Inclusion criteria must be met at the time of screening unless otherwise specified.

Age ≥ 18 years
Solid Tumor: Histologically documented diagnosis of primary or metastatic solid tumors refractory to standard therapy or for which no standard therapy exists. Entry will include, but is not limited to patients with androgen-independent prostate cancer, and cancers of the breast, ovary, head and neck, non-small cell lung, bladder, colorectal or kidney. Lymphoma: Relapsed or refractory B-Cell, T-Cell or NK-Cell lymphoma or Hodgkin's Disease. At Yale Cancer Center, lymphoma patients will be limited to those who are not eligible for potentially curative re-induction regimens and transplant and without a reasonable chance of having durable remissions with standard therapies.
At least one evaluable lesion. Lesions must be evaluated by CT-scan, MRI, or bone scan. Patients with prostate cancer, bone disease and rising PSA but no other evaluable disease are eligible and will be evaluated based on PSA. For lymphoma patients, lesions can also be measured by PET and/or evaluated in peripheral blood or bone marrow.
Progressive disease: Progressive disease will be defined as new or progressive lesions on CT-scan, MRI, bone scan or by rising PSA (see Section 11.3).
≥ 4 weeks since prior RT or chemotherapy.
Karnofsky Performance Status ≥ 60%
Solid Tumor: Acceptable liver, renal and bone marrow function including the following:
Absolute neutrophil count ≥ 1.5 x 109/L
Hemoglobin ≥ 9.0 g/dl
Platelets ≥ 100 x 109/L
Bilirubin ≤ 1.5 times the upper limit of normal (x ULN)
Aspartate transaminase (AST) and alanine transaminase (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 in the therapeutic range if on anticoagulation therapy
Lymphoma: Acceptable liver, renal and bone marrow function including the following:
Absolute Neutrophil Count ≥ 1.0 x 109/L
Platelets ≥ 50 x 109/L
Bilirubin ≤ 1.5 times the upper limit of normal (x ULN), or ≤ 3 times ULN if documented hepatic involvement with lymphoma, or ≤ 5 times ULN if history of Gilbert's disease
Aspartate transaminase (AST) and alanine transaminase (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 in the therapeutic range if on anticoagulation therapy
Serum potassium within normal range
Estimated life expectancy greater than 3 months
Signed informed consent must be obtained prior to any study specific procedures

Exclusion Criteria

Patients who meet any of the following criteria are not eligible to enroll in this trial:

Prior treatment with PXD101
Solid Tumor: Anticancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the last 4 weeks or a longer period depending on the defined characteristics of the agents used (e.g. 6 weeks for mitomycin or nitrosourea) Lymphoma: No anticancer therapy within 2 weeks except for Rituximab which patients should be off for greater than three months unless there is evidence of disease progression.
Lymphoma patients who have relapsed within 100 days of autologous or allogeneic transplantation.
Serious concomitant systemic disorders (eg, active infection) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
Presence of metastatic disease that, in the opinion of the investigator, would require palliative treatment within 4 weeks of enrollment
Symptomatic brain metastases
Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, a condition requiring anti-arrhythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry
A marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval >500 msec; Long QT Syndrome; the required use of concomitant medication on PXD101 dosing days that may cause Torsade de Pointes (See Section 11.7)
Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
Pregnant or breast-feeding women
Men and women of childbearing age and potential, who are not willing to use effective contraception
Major surgery within the last 4 weeks
Known HIV positivity, as safety in this patient population has not been assessed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale New Haven Hospital	New Haven	Connecticut	United States	06520
2	Columbia University - Herbert Irving Cancer Center	New York	New York	United States	01132
3	New York University Cancer Institute	New York	New York	United States	10016
4	M.D. Anderson Cancer Center	Houston	Texas	United States	77230-1402
5	Research Facility	Copenhagen		Denmark
6	Research Facility	London	Surrey	United Kingdom	SW3 6JJ