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):
Onxeo
ClinicalTrials.gov Identifier:
NCT00421889
First received: January 12, 2007
Last updated: July 7, 2015
Last verified: July 2015
Results First Received: July 1, 2014  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Ovarian Cancer
Epithelial Ovarian Cancer
Fallopian Tube Cancer
Bladder Cancer
Interventions: Drug: belinostat
Drug: Paclitaxel
Drug: Carboplatin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Part A: Dose Escalation 600/5/NA PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 (area under the curve) administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 0 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part A: Dose Escalation 600/NA/175 PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part A: Dose Escalation 600/5/175 PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part A: Dose Escalation 800/5/175 PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part A: Dose Escalation 1000/5/175 PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part B: Ovarian Cancer MTD PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
Part D: Bladder Cancer MTD PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3

Participant Flow:   Overall Study
    Part A: Dose Escalation 600/5/NA     Part A: Dose Escalation 600/NA/175     Part A: Dose Escalation 600/5/175     Part A: Dose Escalation 800/5/175     Part A: Dose Escalation 1000/5/175     Part B: Ovarian Cancer MTD     Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer     Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer     Part D: Bladder Cancer MTD  
STARTED     5     5     3     4     6     35     4     3     15  
COMPLETED     0 [1]   0 [2]   0 [3]   0 [4]   0 [5]   0 [6]   0 [7]   1 [3]   4 [8]
NOT COMPLETED     5     5     3     4     6     35     4     2     11  
Adverse Event                 1                 0                 1                 1                 1                 4                 1                 0                 2  
Withdrawal by Subject                 1                 3                 0                 0                 2                 0                 0                 0                 0  
Death                 0                 0                 0                 0                 1                 1                 0                 0                 0  
Progressive disease                 3                 2                 2                 3                 2                 21                 3                 1                 5  
Patient/Investigator request                 0                 0                 0                 0                 0                 9                 0                 1                 3  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 0                 0                 1  
[1] Mean number of PXD101 cycles administered: 5.20
[2] Mean number of PXD101 cycles administered: 8.20
[3] Mean number of PXD101 cycles administered: 3.33
[4] Mean number of PXD101 cycles administered: 9.25
[5] Mean number of PXD101 cycles administered: 5.00
[6] Mean number of PXD101 cycles administered: 7.69
[7] Mean number of PXD101 cycles administered: 5.50
[8] Mean number of PXD101 cycles administered: 4.27



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Part A: Dose Escalation 600/5/NA PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 0 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part A: Dose Escalation 600/NA/175 PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part A: Dose Escalation 600/5/175 PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part A: Dose Escalation 800/5/175 PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part A: Dose Escalation 1000/5/175 PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part B: Ovarian Cancer MTD PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
Part D: Bladder Cancer MTD PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
Total Total of all reporting groups

Baseline Measures
    Part A: Dose Escalation 600/5/NA     Part A: Dose Escalation 600/NA/175     Part A: Dose Escalation 600/5/175     Part A: Dose Escalation 800/5/175     Part A: Dose Escalation 1000/5/175     Part B: Ovarian Cancer MTD     Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer     Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer     Part D: Bladder Cancer MTD     Total  
Number of Participants  
[units: participants]
  5     5     3     4     6     35     4     3     15     80  
Age  
[units: participants]
                   
<=18 years     0     0     0     0     0     0     0     0     0     0  
Between 18 and 65 years     5     4     3     4     6     22     4     3     8     59  
>=65 years     0     1     0     0     0     13     0     0     7     21  
Gender  
[units: participants]
                   
Female     2     1     3     0     3     35     3     1     4     52  
Male     3     4     0     4     3     0     1     2     11     28  



  Outcome Measures
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1.  Primary:   Maximum Tolerable Dose (MTD) Belinostat, Part A,   [ Time Frame: Cycle 1 ]

2.  Primary:   Dose Limiting Toxicities (DLT), Part A   [ Time Frame: Cycle 1 ]

3.  Secondary:   Best Overall Response (CR or PR)   [ Time Frame: Throughout study until PD (progressive disease) or lost to follow up ]

4.  Secondary:   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 ]

5.  Secondary:   Time to Progression   [ Time Frame: Throughout study ]

6.  Secondary:   Time to Response   [ Time Frame: Throughout study ]

7.  Secondary:   Duration of Response   [ Time Frame: Throughout study ]

8.  Secondary:   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 ]

9.  Secondary:   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 ]

10.  Secondary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: PRS Administrator Gunilla Emanuelson
Organization: Topotarget A/S
phone: +45 39 17 83 92
e-mail: enquiries@topotarget.com



Responsible Party: Onxeo
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: July 7, 2015
Health Authority: United States: Food and Drug Administration
Denmark: Danish Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency