Clinical Trial Results:
Veliparib (ABT888) Monotherapy for Patients with BRCA germline mutation and Platinum-Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer
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Summary
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EudraCT number |
2011-002099-18 |
Trial protocol |
DK |
Global end of trial date |
29 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Dec 2021
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First version publication date |
03 Dec 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
Veli-BRCA
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01472783 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Vejle Hospital
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Sponsor organisation address |
Beriderbakken 4, Vejle, Denmark, 7100
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Public contact |
Clinical Trial Unit, Vejle Hospital, kfe.onko@rsyd.dk
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Scientific contact |
Clinical Trial Unit, Vejle Hospital, kfe.onko@rsyd.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Feb 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Jan 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Jan 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Phase I:
To determine:
• Maximum-tolerated dose (MTD)
• Dose-limiting toxicities (DLT)
• Recommended phase II dose
Phase II:
To investigate the response rate in platinum-resistant and partially platinum sensitive ovarian cancer patients with known BRCA mutations treated with veliparib monotherapy.
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Protection of trial subjects |
Patients were offered antiemetics to treat potential veliparib-induced nausea and vomiting.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 49
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Worldwide total number of subjects |
49
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EEA total number of subjects |
49
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
39
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
The phase I part of the study accrued patients from November 2011 to August 2012 and continued in phase II from September 2012 to March 2015 with enrollment of a total of 48 patients, 16 patients in phase I and 32 patients in phase II. | ||||||
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Pre-assignment
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Screening details |
The phase II was intended to include 33 patients according to protocol, but 1 patient was withdrawn after inclusion because pathology and chart review revealed that her primary diagnosis was not OC but endometrial cancer, and she was withdrawn because of this protocol violation. Most of the included patients were heavily pretreated. | ||||||
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Period 1
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Period 1 title |
Study periode (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Phase II arm | ||||||
Arm description |
The phase II included patients from September 2012 to March 2015 with enrollment of a 32 patients in phase II. The phase II was intended to include 33 patients according to protocol, but 1 patient was withdrawn after inclusion because pathology and chart review revealed that her primary diagnosis was not OC but endometrial cancer, and she was withdrawn because of this protocol violation. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Veliparib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Patients received oral veliparib twice daily on days 1 to 28 (4-weekly treatment cycle). The starting dose in the phase I dose escalating study was 300 mg twice a day (BID)
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End points reporting groups
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Reporting group title |
Phase II arm
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Reporting group description |
The phase II included patients from September 2012 to March 2015 with enrollment of a 32 patients in phase II. The phase II was intended to include 33 patients according to protocol, but 1 patient was withdrawn after inclusion because pathology and chart review revealed that her primary diagnosis was not OC but endometrial cancer, and she was withdrawn because of this protocol violation. | ||
Subject analysis set title |
Response rate
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Overall response: Combined CA125 biomarker and RECIST response.
Tumor assessment was performed at baseline and after every third cycle by computed tomography scans of chest, abdomen, and pelvis according to RECIST version 1.1 and by CA-125 GCIG-modified criteria every third cycle. Response and progression were determined by using the definitions incorporating RECIST 1.1 and CA-125 as agreed by the GCIG. Patients were not evaluable (NE) by RECIST if they had no measurable target lesions according to RECIST version 1.1 (then patients could be included only if they had CA-125 measurable disease), and patients were NE by CA-125 RECIST criteria if their baseline CA-125 value was less than 70 kU/L and could vice versa be enrolled in the protocol only if they had RECIST-measurable disease.
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Subject analysis set title |
PFS
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Progression-free survival was measured from date of first dose of study treatment to progression or death, whichever came first.
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Subject analysis set title |
OS
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Overall survival was calculated from date of first dose of study treatment to date of death of any cause.
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End point title |
Response rate [1] | ||||||||||||||||||||||||
End point description |
Overall response: Combined CA125 biomarker and RECIST response.
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End point type |
Primary
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End point timeframe |
Tumor assessment was performed at baseline and after every third cycle by computed tomography scans of chest, abdomen, and pelvis according to RECIST version 1.1 and by CA-125 GCIG-modified criteria every third cycle.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary endpoint is descriptive and there is no comparisons and therefore no p-values. Simon’s 2-stage minimax design was used for assessment of the phase II part of the trial. The target level for response was set at 40% and 20% as the lower level of clinical interest. With a significance level of 5% and a power of 80%, the trial was planned to include 18 patients in the first step (stage I). If more than 10 patients among the 33 patients responded, the trrialwas defined as sufficiently p |
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| Notes [2] - Response rate only included for phase II part of the study (N=32) |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Progression free survival (PFS) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Progression-free survival was measured from date of first dose of study treatment to progression or death, whichever came first.
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| Notes [3] - PFS calculated for the phase II part of the trial. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall survival (OS) | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Overall survival was calculated from date of first dose of study treatment to date of death of any cause
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Adverse events information
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Timeframe for reporting adverse events |
From trial initiation on Nov 1, 2011 to Feb 1, 2016.
Date of Death was followed beyond 2016 until death of all included subjects.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
Toxicity
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/28763368 |
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