A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment
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.
|Ovarian Cancer Epithelial Ovarian Cancer Fallopian Tube Cancer Bladder Cancer||Drug: belinostat Drug: Paclitaxel Drug: Carboplatin||Phase 1 Phase 2|
|Study Design:||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|
- 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).
- 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.
- 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
- 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 ]
- 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
- 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.
- 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.
- 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 ]
- 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 ]
- 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 ]
|Study Start Date:||August 2005|
|Study Completion Date:||February 2009|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
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
Other Name: PXD101Drug: Paclitaxel Drug: Carboplatin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00421889
|United States, California|
|Gynecologic Oncology Associates|
|Newport Beach, California, United States, 92663|
|United States, Florida|
|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|
|The Finsen Center, Rigshospitalet|
|Copenhagen, Denmark, 2100|
|Research Facility, Herlev University Hospital|
|Herlev, Denmark, 2730|
|The Beatson West of Scotland Cancer Centre|
|Glasgow, United Kingdom, G120YN|
|The Royal Marsden NHS Trust|
|Surrey, United Kingdom, SM2 5PT|
|Study Director:||e-mail contact via email@example.com||Onxeo|