A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
TopoTarget A/S
ClinicalTrials.gov Identifier:
NCT00421889
First received: January 12, 2007
Last updated: November 29, 2013
Last verified: November 2013
  Purpose

The study seeks to assess the safety, pharmacodynamics, pharmacokinetics and efficacy of belinostat (PXD101) administered in combination with carboplatin or paclitaxel or both in patients with solid tumours followed by maximum tolerated dose (MTD) expansion (phase II) in ovarian and bladder cancer patients

The clinical trial is now in the MTD (phase II) portion of the study enrolling bladder cancer patients. Enrollment of ovarian patients is complete.


Condition Intervention Phase
Ovarian Cancer
Epithelial Ovarian Cancer
Fallopian Tube Cancer
Drug: belinostat
Drug: Paclitaxel
Drug: Carboplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Safety, Pharmacodynamic, and Pharmacokinetic Study of Intravenously Administered PXD101 Plus Carboplatin or Paclitaxel or Both in Patients With Advanced Solid Tumours

Resource links provided by NLM:


Further study details as provided by TopoTarget A/S:

Primary Outcome Measures:
  • To determine the maximum tolerated dose and dose limiting toxicities of belinostat (PXD101) administered in combination with standard doses of carboplatin or paclitaxel or both. [ Time Frame: throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the pharmacokinetics of belinostat and its effect on carboplatin and paclitaxel pharmacokinetics [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  • To determine the pharmacodynamic effects of belinostat (in the combination) on histone acetylation in peripheral blood mononuclear cells (selected sites) [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  • To explore the anti-tumor activity (in the combination) in patients with ovarian cancer in need of relapse treatment [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  • To explore the anti-tumor activity (in the combination) in patients with bladder cancer [ Time Frame: throughout the study ] [ Designated as safety issue: No ]

Enrollment: 85
Study Start Date: August 2005
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm Drug: belinostat
1000 mg/m2 days 1-5 in a 21 day cycle; IV
Other Name: PXD101
Drug: Paclitaxel
administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle
Drug: Carboplatin
administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle

Detailed Description:

MTD Expansion I(Phase II): A total of 18-32 patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumours of ovarian origin, in need of relapse treatment will be enrolled.

MTD Expansion II (phase II): A total of 15 patients with urothelial (transitional cell) carcinoma of the bladder will be enrolled.

  Eligibility

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

Inclusion Criteria:

  • Ovarian patients:

    -- Patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian cancer of ovarian origin in need of relapse treatment

  • Bladder patients:

    -- Patients with urothelial (transitional cell) cancer of the bladder

  • All Patients:

    • At least one measurable uni-dimensional lesion
    • ECOG (Eastern Cooperative Oncology Group) status ≤ 2
    • Life expectancy ≥ 3 months
    • Age ≥ 18 years
    • Acceptable liver, renal and bone marrow function:

      • Bilirubin ≤ 1.5 x ULN (upper limit of normal)
      • AST (SGOT) (aspartate aminotransferase), ALT (SGPT) (alanine aminotransferase)and Alkaline Phosphatase ≤ 3 x ULN. If liver metastases are present then ≤ 5 x ULN is allowed.
      • Measured EDTA (ethylenediaminetetraacetic acid) renal clearance ≥ 45 mL/min (within EU).
      • Creatinine clearance ≥ 45 mL/min (within USA)
    • Leucocytes > 2.5 x 109/ L
    • Neutrophils > 1.0 x 109/L
    • Platelets > 100 x 109/L
    • Hemoglobin > 9.0 g/dL or > 5.6 mmol/l
    • Acceptable coagulation status
    • Negative pregnancy test/use of effective contraceptive methods for women of childbearing potential.
    • Serum potassium within normal range

Exclusion Criteria:

  • More than three prior lines of chemotherapy given for metastatic disease
  • History of a concurrent second malignancy
  • History of hypersensitivity to either platinum or paclitaxel that cannot be desensitized
  • Co-existing active infection or any co-existing medical condition likely to interfere with trial procedures, including:

    • significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease)
    • myocardial infarction within the past 6 months
    • unstable angina
    • congestive heart failure requiring therapy
    • unstable arrhythmia or a need for anti-arrhythmic therapy
    • evidence of ischemia on ECG
    • marked baseline prolongation of QT/QTc ((corrected)QT interval) interval, e.g., repeated demonstration of a QTc interval > 500 msec;
    • long QT Syndrome
    • required use of concomitant medication on PXD101 infusion days that may cause Torsade de Pointes.
  • Bowel obstruction or impending bowel obstruction
  • Known HIV positivity
  • Mixed mullerian cancer of intra-uterine origin
  • Any existing grade 2 or above drug-related neurotoxicity due to prior treatment with agents causing neurotoxicity
  • Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
  • Treatment with investigational agents within the last 4 weeks
  • Prior anticancer therapy within the last 3 weeks of trial dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy
  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: NCT00421889

Locations
United States, California
Gynecologic Oncology Associates
Newport Beach, California, United States, 92663
United States, Florida
Research Facility
Orlando, Florida, United States, 32804
United States, Louisiana
Hematology and Oncology Specialists, LLC
Covington, Louisiana, United States, 70433
Hematology & Oncology Specialists, LLC
Metairie, Louisiana, United States, 70006
United States, Maryland
Greater Baltimore Medical Center
Baltimore, Maryland, United States, 21204
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Rhode Island
Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
Denmark
The Finsen Center, Rigshospitalet
Copenhagen, Denmark, 2100
Research Facility
Herlev, Denmark, 2730
United Kingdom
The Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom, G120YN
The Royal Marsden NHS Trust
Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
TopoTarget A/S
  More Information

No publications provided

Responsible Party: TopoTarget A/S
ClinicalTrials.gov Identifier: NCT00421889     History of Changes
Other Study ID Numbers: PXD101-CLN-8, PXD101-040-EU
Study First Received: January 12, 2007
Last Updated: November 29, 2013
Health Authority: United States: Food and Drug Administration
Denmark: Danish Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by TopoTarget A/S:
Ovarian cancer
Ovarian Neoplasms
Primary peritoneal
Epithelial ovarian
Fallopian tube
belinostat
PXD101
mixed mullerian cancer of ovarian origin

Additional relevant MeSH terms:
Ovarian Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Neoplasms by Histologic Type
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 23, 2014