UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000046007 |
|---|---|
| Receipt number | R000052482 |
| Scientific Title | A translational study on mechanism of resistance to PARP inhibitor in patients with breast cancer and gBRCA1/2 mutation (WJOG15321B) |
| Date of disclosure of the study information | 2021/11/09 |
| Last modified on | 2026/04/18 09:39:06 |
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Basic information
Public title
A translational study on mechanism of resistance to PARP inhibitor in patients with breast cancer and gBRCA1/2 mutation (WJOG15321B)
Acronym
OLIVE
Scientific Title
A translational study on mechanism of resistance to PARP inhibitor in patients with breast cancer and gBRCA1/2 mutation (WJOG15321B)
Scientific Title:Acronym
OLIVE
Region
| Japan |
Condition
Condition
germline BRCA1/2 mutation-positive metastatic breast cancer
Classification by specialty
| Hematology and clinical oncology | Breast surgery |
Classification by malignancy
Malignancy
Genomic information
YES
Objectives
Narrative objectives1
To evaluate frequency of true reversion BRCA1/2 mutation in gBRCA1/2-mutated metastatic breast cancer patients with acquired resistance to olaparib
Basic objectives2
Others
Basic objectives -Others
To examine whether cytotoxic chemotherapy induces BRCA1/2 reversion mutations in gBRCA1/2 mutated primary breast cancer patients
Trial characteristics_1
Trial characteristics_2
Developmental phase
Assessment
Primary outcomes
Frequency of BRCA1/2 reversion mutation in tumors with acquired resistance to olaparib
Key secondary outcomes
-Frequency of acquired resistance to olaparib by mechanisms other than reversion mutations, including 53BP1 loss, PTIP loss, SLFN11 loss, and PARG loss
-Function of BRCA1/2 in cases of putative BRCA1/2 reversion mutations
-Differences in the frequency of reversion mutations in BRCA1/2 by number of previous chemotherapy to olaparib
Base
Study type
Observational
Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 20 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
1) HER2 negative (HER2 IHC score of 0, 1 + or 2 + with FISH negative)
2)Positive for gBRCA1/2 mutations, limited to deleterious or suspected deleterious mutations only, not variants of uncertain significance (VUS)
3) Metastatic or unresectable locally advanced breast cancer
4) Falling under any of the following categories,
(a) Plan to initiate olaparib treatment
(b) Currently being treated with olaparib
(c) Previously treated with olaparib
5) No prior use of PARP inhibitors other than olaparib
6) Aged 20 years or older at the time of obtaining consent
7) One or more measurable or non-measurable lesions found in computed tomography (CT) scan or magnetic resonance imaging (MRI) taken within 30 days of olaparib administration
8) Has provided informed consent to participate in this study
Key exclusion criteria
Any subject deemed unsuitable by the principal investigator or sub-investigator
Target sample size
60
Research contact person
Name of lead principal investigator
| 1st name | Hitomi |
| Middle name | |
| Last name | Sakai |
Organization
Showa University
Division name
Advanced Cancer Translational Research Institute
Zip code
142-8666
Address
1-5-8 Hatanodai, Shinagawa-ku, Tokyo
TEL
03-3784-8146
sakai-h@med.showa-u.ac.jp
Public contact
Name of contact person
| 1st name | Shinichiro |
| Middle name | |
| Last name | Nakamura |
Organization
West Japan Oncology Group
Division name
WJOG datacenter
Zip code
556-0016
Address
Namba Plaza Bldg. 304-1-5-7, Motomachi Naniwa-ku, Osaka
TEL
06-6633-7400
Homepage URL
datacenter@wjog.jp
Sponsor or person
Institute
West Japan Oncology Group
Institute
Department
Personal name
Funding Source
Organization
AstraZeneca K.K.
Organization
Division
Category of Funding Organization
Profit organization
Nationality of Funding Organization
JAPAN
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Showa University Research Ethics Review Board
Address
1-5-8 Hatanodai, Shinagawa-ku, Tokyo
Tel
03-3784-8129
m-rinri@ofc.showa-u.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
Other administrative information
Date of disclosure of the study information
| 2021 | Year | 11 | Month | 09 | Day |
Related information
URL releasing protocol
https://doi.org/10.1007/s12282-026-01855-2
Publication of results
Published
Result
URL related to results and publications
https://doi.org/10.1007/s12282-026-01855-2
Number of participants that the trial has enrolled
60
Results
From Nov 2021 to Oct 2023, 60 patients were enrolled (median age 50.5). BRCA1 20%, BRCA2 80%. Median prior therapies: 2. In progressed cases with ctDNA, reversion mutations were 25% (BRCA1) and 23.5% (BRCA2). One case showed detection 7 months before progression. Most involved secondary indels; none in the C-terminal region.
Results date posted
| 2026 | Year | 04 | Month | 18 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
| 2026 | Year | 04 | Month | 10 | Day |
Baseline Characteristics
Among 60 patients, germline BRCA1 mutations were present in 20.0% and BRCA2 mutations in 80.0%. Prior treatments included platinum in 2 patients and anthracyclines in 42 patients.
Participant flow
From November 2021 to October 2023, 60 patients were enrolled. Germline BRCA1 mutations were present in 20.0% and BRCA2 mutations in 80.0%. Prior treatments included platinum in 2 patients and anthracyclines in 42 patients. During the observation period, 75% (45/60) discontinued olaparib, all due to disease progression. The median treatment duration was 11.7 months (95% CI: 9.0 to 13.1). Baseline blood samples were collected from all patients, and post-treatment samples were obtained from 42 patients.
Adverse events
NE
Outcome measures
Primary endpoint: Incidence of BRCA1/2 reversion mutations.
Among patients who experienced disease progression during olaparib treatment and had available ctDNA analysis, BRCA1 reversion mutations were detected in 25.0% (2/8), and BRCA2 reversion mutations in 23.5%
Plan to share IPD
The data that support the findings of this study are available from the corresponding author upon reasonable request.
IPD sharing Plan description
Progress
Recruitment status
Main results already published
Date of protocol fixation
| 2021 | Year | 09 | Month | 17 | Day |
Date of IRB
| 2021 | Year | 09 | Month | 30 | Day |
Anticipated trial start date
| 2021 | Year | 11 | Month | 19 | Day |
Last follow-up date
| 2024 | Year | 05 | Month | 18 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
| 2026 | Year | 05 | Month | 31 | Day |
Other
Other related information
To evaluate frequency of true reversion BRCA1/2 mutation in gBRCA1/2-mutated metastatic breast cancer patients with acquired resistance to olaparib
Management information
Registered date
| 2021 | Year | 11 | Month | 08 | Day |
Last modified on
| 2026 | Year | 04 | Month | 18 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000052482
