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

July 7, 2015 updated by: Onxeo

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: Carboplatin
Drug: Paclitaxel
Drug: belinostat
Other Names:
  • PXD101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerable Dose (MTD) Belinostat, Part A,
Time Frame: Cycle 1
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).
Cycle 1
Dose Limiting Toxicities (DLT), Part A
Time Frame: Cycle 1
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.
Cycle 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Overall Response (CR or PR)
Time Frame: Throughout study until PD (progressive disease) or lost to follow up
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
Throughout study until PD (progressive disease) or lost to follow up
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
Throughout the study
Time to Progression
Time Frame: Throughout study
Time to progression, defined as the interval between the first dates of treatment until the first notation of disease progression. RECIST criteria
Throughout study
Time to Response
Time Frame: Throughout study
Time to response (RECIST) was assessed as the interval between the first dates of treatment until the first notation of response.
Throughout study
Duration of Response
Time Frame: Throughout study
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.
Throughout study
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
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
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
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
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Onxeo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2005

Primary Completion (ACTUAL)

February 1, 2009

Study Completion (ACTUAL)

February 1, 2009

Study Registration Dates

First Submitted

January 12, 2007

First Submitted That Met QC Criteria

January 12, 2007

First Posted (ESTIMATE)

January 15, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

July 28, 2015

Last Update Submitted That Met QC Criteria

July 7, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PXD101-CLN-8
  • PXD101-040-EU

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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