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

This study has been completed.
Sponsor:
Collaborator:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
TopoTarget A/S
ClinicalTrials.gov Identifier:
NCT00413075
First received: December 18, 2006
Last updated: November 12, 2014
Last verified: November 2014
  Purpose

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 Intervention Phase
Solid Tumor
Lymphoma
Drug: oral belinostat
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Dose Escalation Trial of Oral PXD101 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by TopoTarget A/S:

Primary Outcome Measures:
  • Safety, tolerability and maximum tolerated dose of orally administered PXD101 for each cohort [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the pharmacokinetics of oral PXD101 when dosed once or twice daily at various dose levels [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  • Explore anti-tumor activity [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  • Determine the safety, tolerability, and anti-tumor activity of orally administered PXD101 to patients with lymphoma [ Time Frame: throughout the trial ] [ Designated as safety issue: Yes ]

Enrollment: 121
Study Start Date: June 2006
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: oral belinostat Drug: oral belinostat
oral belinostat dosed once or twice daily at continuous and discontinuous dosing schedules.
Other Name: PXD101

  Eligibility

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00413075

Locations
United States, Connecticut
Yale New Haven Hospital
New Haven, Connecticut, United States, 06520
United States, New York
Columbia University - Herbert Irving Cancer Center
New York, New York, United States, 01132
New York University Cancer Institute
New York, New York, United States, 10016
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77230-1402
Denmark
Research Facility
Copenhagen, Denmark
United Kingdom
Research Facility
London, Surrey, United Kingdom, SW3 6JJ
Sponsors and Collaborators
TopoTarget A/S
Spectrum Pharmaceuticals, Inc
Investigators
Study Chair: enquiries@topotarget.com TopoTarget A/S
  More Information

No publications provided

Responsible Party: TopoTarget A/S
ClinicalTrials.gov Identifier: NCT00413075     History of Changes
Obsolete Identifiers: NCT00411476
Other Study ID Numbers: PXD101-CLN-9
Study First Received: December 18, 2006
Last Updated: November 12, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Denmark: Danish Medicines Agency

Keywords provided by TopoTarget A/S:
Solid tumors
Adenosarcoma
B-cell lymphoma
belinostat
bladder cancer
Breast cancer
Carcinoma, Non-Small-Cell Lung
Carcinoma, Small Cell
Chondrosarcoma
colorectal cancer
Esophageal Neoplasms
Fibrosarcoma
head and neck cancer
Hemangiosarcoma
Hodgkins Disease
kidney cancer
Leiomyosarcoma
Liposarcoma
lung cancer
lymphoma
mesothelioma
mesothelioma, cystic
Mixed Tumor, Mesodermal
Osteosarcoma
Otorhinolaryngologic Neoplasms
Ovarian cancer
Parathyroid Neoplasms
Prostate cancer
sarcoma
T-cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Belinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014