NCT00413075

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
121

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jun 2006

Longer than P75 for phase_1

Geographic Reach
3 countries

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2006

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

December 18, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 19, 2006

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2011

Completed
Last Updated

July 8, 2015

Status Verified

July 1, 2015

Enrollment Period

5.2 years

First QC Date

December 18, 2006

Last Update Submit

July 7, 2015

Conditions

Solid TumorLymphoma

Keywords

Solid tumorsAdenosarcomaB-cell lymphomabelinostatbladder cancerBreast cancerCarcinoma, Non-Small-Cell LungCarcinoma, Small CellChondrosarcomacolorectal cancerEsophageal NeoplasmsFibrosarcomahead and neck cancerHemangiosarcomaHodgkins Diseasekidney cancerLeiomyosarcomaLiposarcomalung cancerlymphomamesotheliomamesothelioma, cysticMixed Tumor, MesodermalOsteosarcomaOtorhinolaryngologic NeoplasmsOvarian cancerParathyroid NeoplasmsProstate cancersarcomaT-cell lymphomathyroid cancerPXD101

Outcome Measures

Primary Outcomes (1)

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

    throughout the study

Secondary Outcomes (3)

  • 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

Study Arms (1)

oral belinostat

EXPERIMENTAL
Drug: oral belinostat

Interventions

oral belinostatDRUG

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

Also known as: PXD101
oral belinostat

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • +9 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Columbia University - Herbert Irving Cancer Center

New York, New York, 01132, United States

Location

New York University Cancer Institute

New York, New York, 10016, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77230-1402, United States

Location

Research Facility

Copenhagen, Copenhagen, Denmark

Location

Research Facility

London, Surrey, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

LymphomaAdenosarcomaLymphoma, B-CellUrinary Bladder NeoplasmsBreast NeoplasmsCarcinoma, Non-Small-Cell LungCarcinoma, Small CellChondrosarcomaColorectal NeoplasmsEsophageal NeoplasmsFibrosarcomaHead and Neck NeoplasmsHemangiosarcomaHodgkin DiseaseKidney NeoplasmsLeiomyosarcomaLiposarcomaLung NeoplasmsMesotheliomaMesothelioma, CysticMixed Tumor, MesodermalOsteosarcomaOtorhinolaryngologic NeoplasmsOvarian NeoplasmsParathyroid NeoplasmsProstatic NeoplasmsSarcomaLymphoma, T-CellThyroid Neoplasms

Interventions

belinostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNeoplasms, Complex and MixedNeoplasms, Connective and Soft TissueLymphoma, Non-HodgkinUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesCarcinoma, BronchogenicBronchial NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesCarcinomaNeoplasms, Glandular and EpithelialNeoplasms, Connective TissueIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesEsophageal DiseasesNeoplasms, Fibrous TissueNeoplasms, Vascular TissueKidney DiseasesNeoplasms, Muscle TissueNeoplasms, Adipose TissueAdenomaNeoplasms, MesothelialNeoplasms, Bone TissueOtorhinolaryngologic DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleGenital Neoplasms, FemaleGenital DiseasesEndocrine System DiseasesGonadal DisordersParathyroid DiseasesGenital Neoplasms, MaleGenital Diseases, MaleProstatic DiseasesThyroid Diseases

Study Officials

  • enquiries@topotarget.com

    Valerio Therapeutics

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 18, 2006

First Posted

December 19, 2006

Study Start

June 1, 2006

Primary Completion

August 1, 2011

Study Completion

August 1, 2011

Last Updated

July 8, 2015

Record last verified: 2015-07

Locations

GB(1)DK(1)US(4)