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: December 5, 2014
Last verified: December 2014
  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
Bladder 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:
  • Maximum Tolerable Dose (MTD) Belinostat, Part A, [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]
    To determine the maximum tolerated dose of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin (AUC of 5) and paclitaxel (175 mg/m2).

  • Dose Limiting Toxicities (DLT), Part A [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]
    To determine the number of participants experiencing dose limiting toxicities of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin and paclitaxel or both.


Secondary Outcome Measures:
  • Best Overall Response (CR or PR) [ Time Frame: Throughout study until PD (progressive disease) or lost to follow up ] [ Designated as safety issue: No ]
    Best overall responses were assessed by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Clinical tumor evaluation will take place after each cycle. Formal radiological evaluation after every 2 cycles. If a response is noted, a follow-up radiographic assessment must be performed 4 weeks (+ 1 week) after the response is noted

  • 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 ]
  • Time to Progression [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
    Time to progression, defined as the interval between the first dates of treatment until the first notation of disease progression. RECIST criteria

  • Time to Response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
    Time to response (RECIST) was assessed as the interval between the first dates of treatment until the first notation of response.

  • Duration of Response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
    Defined as interval from the time criteria for CR or PR are met, until the first date that recurrent or progressive disease is objectively documented.

  • Belinostat Cmax [ Time Frame: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h ] [ Designated as safety issue: No ]
  • Belinostat Mean t½ [ Time Frame: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h ] [ Designated as safety issue: No ]
  • Belinostat AUC (0-infinity) [ Time Frame: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h ] [ Designated as safety issue: No ]

Enrollment: 80
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

Belinostat: 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: Administered IV 2-3 hours after belinostat infusion on day 3 in a 21-day cycle

Carboplatin: Administered IV infusion after paclitaxel on day 3 in a 21-day cycle

Drug: belinostat
Other Name: PXD101
Drug: Paclitaxel Drug: Carboplatin

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:

  1. Signed consent of an IRB (Institutional Review Board) approved consent form.
  2. Patients with histologically confirmed solid carcinomas, for which there is no known curative therapy.
  3. Performance status (Eastern Cooperative Oncology Group [ECOG]) ≤ 2.
  4. Life expectancy of at least 3 months.
  5. Age ≥ 18 years.
  6. Acceptable liver, renal and bone marrow function including the following:

    1. Bilirubin ≤ 1.5 times ULN (upper limit of normal).
    2. AST/SGOT ([Aspartate Amino Transferase/Serum glutamic oxaloacetic transaminase]), ALT/SGPT ([Alanine Amino Transferase/Serum glutamic pyruvic transaminase]) and alkaline phosphatase ≤ 3 times ULN (if liver metastases are present, then ≤ 5 x ULN is allowed).
    3. Measured EDTA ([ethylenediaminetetraacetic acid]) renal clearance ≥ 45 mL/min (EU sites). At the US sites calculated creatinine clearance ≥ 45 mL/min using the Jeliffe formula.
    4. Leukocytes > 2.5×109/L, neutrophils > 1.0x109/L, platelets > 100×109/L.
    5. Hemoglobin > 9.0 g/dL or > 5.6 mmol/L.
  7. Acceptable coagulation status: PT-INR([prothrombin-International Normalized Ratio])/APTT([Activated Partial Thromboplastin Time]) ≤ 1.5 × ULN or in the therapeutic range if on anticoagulation therapy
  8. A negative pregnancy test for women of childbearing potential. For men and women of child-producing potential, the use of effective contraceptive methods during the study is required.
  9. Serum potassium within normal range (added in protocol Global version 3.0) Additional Eligibility Criteria at the MTD Expansion only
  10. Patients with epithelial ovarian cancer in need of relapse treatment. Changed with protocol Global version 3 to: Patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumors of ovarian origin in need of relapse treatment.

    Or

  11. Patients with urothelial (transitional cell) carcinoma of the bladder who have received up to a maximum of 3 previous chemotherapy regimens in the advanced disease setting (neoadjuvant chemotherapy is not included in the total of chemotherapy regimens), applies only for patients enrolled in Part D.
  12. At least one uni-dimensional measurable lesion. Lesions must be measured by CT scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST)(Added with protocol Global version 4).

    Eligibility Criteria for the Site Specific Amendment (Part C) - Advanced solid tumors only

  13. Patients with refractory solid tumors other than ovarian cancer.

Exclusion Criteria:

  1. Treatment with investigational agents within the last 4 weeks.
  2. Prior anticancer therapy within the last 3 weeks of study dosing including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents. Changed with protocol Global version 1; prior anticancer therapy within the last 3 weeks of study dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy.
  3. Co-existing active infection or any co-existing medical condition likely to interfere with study 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, or evidence of ischemia on ECG, marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval ([corrected QT interval ]) > 500 msec; Long QT Syndrome; the required use of concomitant medication on belinostat infusion days that may cause Torsade de Pointes (see Appendix 1.1, protocol EU version 1.0, Appendix A - Appendix 16.1.1).
  4. Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
  5. History of a concurrent second malignancy. Changed with Site Specific Amendment (Part D) to: History of a concurrent second malignancy. In patients with urothelial (transitional cell) carcinoma of the bladder an exception is that an incidental finding of localized prostate cancer at the time of radical cystectomy does not preclude inclusion in the study. In such cases a patient will be eligible for inclusion if the Gleason score is ≤6 and the Prostate Specific Antigen (PSA) <10 ng/mL (if the patient would be on hormonal treatment the PSA must be undetectable).Only applied to patients included in this site specific amendment.
  6. History of hypersensitivity to either platinum or paclitaxel that is unable to be desensitized (added with protocol Global version 4).
  7. More than 3 prior lines of chemotherapy given for metastatic disease (added with protocol Global version 1).
  8. Bowel obstruction or impending bowel obstruction.
  9. Known HIV positivity.
  10. Any Grade 2 or above drug-related neurotoxicity, following recovery.
  11. Changed with protocol Global version 1 to: Any existing Grade 2 or above drug related neurotoxicity due to prior treatment with agents causing neurotoxicity.

    Additional exclusion criteria at the MTD expansion only

  12. Mixed mullerian tumors of intra-uterine origin, added with protocol Global version 3.
  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 University Hospital
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
Investigators
Study Director: e-mail contact via enquires@topotarget.com 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
Results First Received: July 1, 2014
Last Updated: December 5, 2014
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
Bladder cancer
belinostat
PXD101
mixed mullerian cancer of ovarian origin

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Belinostat
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on March 26, 2015