Clinical Trial Results:
A single arm, open-label, phase II study to assess the efficacy of rucaparib in metastatic breast cancer patients with a BRCAness genomic signature.
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Summary
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EudraCT number |
2015-000580-14 |
Trial protocol |
FR |
Global end of trial date |
09 Jan 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Mar 2022
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First version publication date |
01 Mar 2022
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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 |
UC-0105/1501
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02505048 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UNICANCER
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Sponsor organisation address |
101 rue de Tolbiac, Paris, France, 75013
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Public contact |
Nourredine AIT-RAHMOUNE, UNICANCER, 33 1 71 93 67 04, n.ait-rahmoune@unicancer.fr
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Scientific contact |
Nourredine AIT-RAHMOUNE, UNICANCER, 33 1 71 93 67 04, n.ait-rahmoune@unicancer.fr
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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 |
26 Mar 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jan 2020
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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 |
The primary objective was to assess the clinical benefit rate (CBR) of rucaparib in previously treated metastatic breast cancer patients with a BRCAness profile or a BRCA1/2 somatic mutation, and if significant, to assess the overall response rate (ORR).
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Protection of trial subjects |
An Independent Ethics Committees reviewed and gave a favorable opinion to the study documents, including the initial protocol and all subsequent amendments, and all information and documents provided to subjects/patients.
This study was conducted in accordance with:
* The Declaration of Helsinki (1964) and subsequent amendments
* The Good Clinical Practices defined by the International Conference on Harmonization (ICH–E6, 17/07/96
* The European Directive (2001/20/CE)
* The Huriet’s law (n° 88-1138) of December 20th, 1988, relative to the protection of persons participating in biomedical research and modified by the Public Health Law n°2004-806 of August 9th, 2004,
* The law on ‘informatics and freedom’ (Informatique et Libertés n° 78-17) of January 6th,1978 modified by the law n° 2004-801 of August 6th, 2004 relative to the protection of persons with regard to the computerized processing of personal data
* The bioethic law n°2011-814 of July 8, 2011.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Aug 2015
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
2 Years | ||
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 |
France: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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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) |
29
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
RUBY was a single arm, open-label, multicentric, phase II trial assessing the efficacy of the PARP inhibitor rucaparib. Patients had HER2 negative, BRCAness profile defined by Clovis genomic signature or BRCA1/2 somatic mutation, progressing breast cancer with at least one line of chemotherapy at the metastatic setting. | ||||||||||||
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Pre-assignment
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Screening details |
The study consisted of a 28-day screening phase to establish patients' eligibility and document baseline measurements, a treatment phase (28-day treatment cycles until disease progression), and a long-term follow-up to monitor the clinical benefit rate, progression-free survival, overall survival, and the prognostic value of the Clovis signature. | ||||||||||||
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Period 1
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Period 1 title |
Overall period
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Rucaparib | ||||||||||||
Arm description |
All eligible patients entering the study received rucaparib (600 mg oral) twice daily, every day in 28-day cycles until patient withdrawal (toxicity, disease progression, or after patient’s or investigator’s decision). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Rucaparib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All eligible patients received 600 mg oral rucaparib (2 x 300 mg tablets) twice daily, every day in 28-day cycles until toxicity, disease progression, or patient’s or investigator’s decision. Tablets should have been swallowed with at least 240 mL of water at the same time each morning, and evening without regards to meals.
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Baseline characteristics reporting groups
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Reporting group title |
Overall period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Rucaparib
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Reporting group description |
All eligible patients entering the study received rucaparib (600 mg oral) twice daily, every day in 28-day cycles until patient withdrawal (toxicity, disease progression, or after patient’s or investigator’s decision). | ||
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End point title |
Clinical benefice rate [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
DIsease evolution was assessed every 8 weeks until disease progression (up to 30 moths) according to RECIST evaluation.
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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 was the clinical benefice rate. The decision rule was that least 11 of 37 evaluable patients were required to achieve a clinical response in order to claim for the success of the study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free survival | ||||||||
End point description |
The Progression free survival was defined as the time from first dose of rucaparib to the disease progression assessed by RECIST or death from any cause. Patients still alive at the time of analysis without documented progression were censored at the last tumor assessment.
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End point type |
Secondary
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End point timeframe |
30 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall survival | ||||||||
End point description |
The Overall survival was defined as the delay between the date of inclusion to death from any cause. Patients still alive at the time of analysis (including lost to follow-up) were censored at the last known alive date.
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End point type |
Secondary
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End point timeframe |
30 months
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Overall period of the study (up to 30 months after first study medication intake)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
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Reporting groups
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Reporting group title |
Rucaparib
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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? Yes | |||
Date |
Amendment |
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19 Jun 2015 |
Following the request of the competent authority (ANSM), the sponsor modified the information relative to contraception in the protocol and the patient consent form. A serum pregnancy test was requested before initiation of all treatment cycles. Hormonal contraception were excluded due to potential interactions with rucaparib. |
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17 Jul 2015 |
* The protocol was modified to specifiy the link between SAFIR02 and RUBY studies. Patients not eligible to randomization in the SAFIR02 study (but meeting all the inclusion/exclusion criteria of the RUBY study) may be included.
* Rucaparib in 120 mg tablets were replaced by 200 mg tablets, the first step of the dose modification strategy was modified and the third level of dose reduction implemented to be consistent with other clinical trilas using rucaparib montherapy 600 mg b.i.d, every day in 28-day cycles. |
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30 Jun 2016 |
* Patients were allowed to take 2 x 300mg tablets or 3 x 200 mg tablets.
* Patient who consented to participate to the ancillary study were asked for blood samples. The volume of blood collected was reduced from 30 mL to 20 mL in "Streck” tubes instead of EDTA tubes.
* An independent committee of radiologist was implemented to confirm the investigator radiological-based assessment of rucaparib efficacy.
* The safety section of the protocol was amended following publication of the version7 of rucaparib’s investigator brochure. Particular attention of grade 3 cholesterol increase was recommended. Also, warning were introduced regarding drug-drug interaction between rucaparib and statins. This modification impacted the collection of SAE by the pharmacovigilance unit at UNICANCER.
*Following the publication of the version 7 of rucaparib’s investigator brochure, myelodysplastic syndrome and acute myeloid leukemia were considered adverse events of special interest. |
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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. | |||
| Limitations of the trial are the small number of subjects analysed, the lack of comparison (single arm study) of rucaparib with usual chemotherapy in patients with high genomic instability associated with poor outcome. | |||
