Platinum and Polyadenosine 5'Diphosphoribose Polymerisation Inhibitor for Neoadjuvant Treatment of Triple Negative Breast Cancer and/or Germline BRCA Positive Breast Cancer
PARTNER
Randomised, Phase II/III, 3 Stage Trial to Evaluate the Safety and Efficacy of the Addition of Olaparib to Platinum-based Neoadjuvant Chemotherapy in Breast Cancer Patients With TNBC and/or gBRCA.
1 other identifier
interventional
780
1 country
30
Brief Summary
This neoadjuvant trial for patients with TNBC and/or gBRCA breast cancer, aims to investigate the safety and efficacy (improvement in pathological Complete Response at surgery) of concurrent platinum-based chemotherapy with olaparib an inhibitor of the PARP enzyme (PARPi).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 breast-cancer
Started May 2016
Longer than P75 for phase_2 breast-cancer
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2016
CompletedFirst Submitted
Initial submission to the registry
July 26, 2016
CompletedFirst Posted
Study publicly available on registry
May 12, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2034
ExpectedNovember 14, 2022
November 1, 2022
8.1 years
July 26, 2016
November 9, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Stage 1 - Number of participants with treatment-related adverse events as assessed by NCI CTCAE v4.03.
Primary outcome measure - safety of the addition of olaparib to three weekly carboplatin/weekly paclitaxel chemotherapy.
1 year - when first 25 patients in each research arm who had received at least one dose of Olaparib protocol treatment have completed their protocol treatment.
Stage 2 - pCR rate and completion rate of Olaparib treatment as per protocol.
Primary outcome measure - pCR in each of the two research arms. At the end of stage 2, one of the research treatments will be dropped using the 'pick the winner' method.
15 months - when pathological complete response (pCR) is available for 53 patients in each of two research arms.
Stage 3 - Efficacy analysis based on pCR at surgery. To be assessed by central review of pathology reports.
Primary outcome measure - pCR at surgery after neoadjuvant treatment. pCR rates after neoadjuvant chemotherapy +/- olaparib, defined as no residual invasive carcinoma within the breast (Ductal Carcinoma in situ permitted) AND no evidence of metastatic disease within the lymph nodes.
5.5 years - October 2021 approx.
Secondary Outcomes (13)
pCR at surgery - assessed by review of histopathology slides
Up to 2 years after last patient randomised
PARTNERing Pathway
2 cycles (each lasting 28 days)
Relapse-Free Survival (RFS)
Up to 10 years after last patient is randomised
Breast cancer specific survival (BCSS)
Up to 10 years after last patient is randomised
Distant disease-free survival
Up to 10 years after last patient is randomised
- +8 more secondary outcomes
Other Outcomes (1)
Discovery and validation of markers that can be correlated with outcomes (pCR and RFS).
Up to 15 years after last patient is randomised
Study Arms (3)
Control
ACTIVE COMPARATOR4 cycles of: Paclitaxel 80mg/m2 Day 1, 8 \& 15, every 3 weeks, Carboplatin area under the curve (AUC) 5 Day 1, every 3 weeks
Research 1
EXPERIMENTAL4 cycles of: Paclitaxel 80mg/m2 on Days 1, 8 \& 15 every 3 weeks, Carboplatin AUC 5 Day 1, every 3 weeks, Olaparib oral 150mg twice daily, Day -2 to Day 10 every 3 weeks
Research 2
EXPERIMENTAL4 cycles of: Paclitaxel 80mg/m2 on Days 1, 8 \& 15 every 3 weeks, Carboplatin AUC 5 Day 1, every 3 weeks, Olaparib oral 150mg twice daily, Day 3 to Day 14 every 3 weeks
Interventions
Patients will self-administer Olaparib by mouth. Olaparib tablets should be taken twice daily at the same time each day approximately 12 hours apart.
Paclitaxel I.V. 80mg/m2 in 0.9% sodium chloride 500ml or according to local practice, will be given over 60 minutes on days 1, 8 \& 15, every 3 weeks for 4 cycles. Carboplatin I.V. AUC5 in 5% dextrose 500ml or according to local practice, over 30-60minutes on day 1 every 3 weeks for 4 cycles.
Eligibility Criteria
You may qualify if:
- Aged between 16 and 70.
- Written informed consent, willing and able to comply with the Protocol for the duration of the trial including undergoing treatment and scheduled visits and examinations.
- Histologically confirmed invasive breast cancer.
- ER-negative\*, and HER2-negative\*\* breast cancer (TNBC). Patients will be eligible with any PR status but PR expression must be scored.
- Germline BRCA (gBRCA) mutation positive, HER2 negative, and PgR / ER of any status.
- T1, T2 or T3 tumours.
- T4 tumour of any size with direct extension to (a) chest wall or (b) skin. OR Inflammatory carcinoma with tumour of any size. OR
- Other Locally Advanced Disease:
- Involvement of ipsilateral large or fixed axillary lymph nodes, or infra or supraclavicular nodes (\>10mm diameter or clinical N2 or N3) and primary breast tumour of any diameter.
- Involvement of ipsilateral large or fixed axillary lymph nodes, or infra or supraclavicular nodes (\>10mm diameter, or clinical N2 or N3), without a primary breast tumour identified, the presence of breast cancer in a Lymph Node (LN) must be histopathologically confirmed by LN biopsy.
- Multifocal tumour:
- \- with at least one tumour with a size\>10mm.
- Patients with bilateral disease are eligible to enter the trial provided that both breast disease meets the above criteria.
- Be fit to receive the trial chemotherapy regimen in the opinion of the responsible clinician:
- Adequate bone marrow, hepatic, and renal function. ECOG performance status of 0, or 1.
- +6 more criteria
You may not qualify if:
- T0 tumour in absence of axillary node \>10mm.
- TNBC with a non-basal phenotype which strongly expresses Androgen Receptor.
- Previous or concomitant chemotherapy or biological agents used for the treatment of cancer in the last 5 years.
- Malignancy within the last 5 years except: adequately treated non-melanoma skin cancer; curatively treated in situ cancer of the cervix; ductal carcinoma in situ (DCIS); Stage 1, grade 1 endometrial carcinoma; or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years.
- Patients with myelodysplastic syndrome/acute myeloid leukaemia.
- Evidence of distant metastasis apparent prior to randomisation.
- Patients with uncontrolled seizures.
- Pre-existing sensory or motor neuropathy of CTCAE v4.03, grade ≥2.
- Concomitant use of known potent CYP3A4 inhibitors and inducers. Consider wash-out periods.
- Pregnant or breast feeding women.
- Not suitable for neoadjuvant chemotherapy in the opinion of the responsible clinician.
- Major surgery within 14 days of starting trial treatment and patients must have recovered from any effects of any major surgery.
- Any evidence of other disease or any concomitant medical or psychiatric problems which in the opinion of the Investigator would prevent completion of treatment or follow-up. For example:
- Evidence of severe or uncontrolled cardiac disease Uncontrolled ventricular arrhythmia Recent myocardial infarction (within 12 months) Active infection including Hepatitis B, Hepatitis C and Human Immunodeficiency virus (HIV). Screening for chronic conditions is not required.
- ECG with mean resting QTc \>470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cambridge University Hospitals NHS Foundation Trustlead
- AstraZenecacollaborator
- Cancer Research UKcollaborator
Study Sites (30)
Cambridge University Hospitals NHS Foundation Trust & the University of Cambridge
Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
Queen's Hospital
Burton-on-Trent, Derby, De13 ORB, United Kingdom
The Christie
Manchester, Lancs, M20 4GJ, United Kingdom
Pinderfields General Hospital
Wakefield, Yorkshire, WF1 4DG, United Kingdom
University Hospital Ayr
Ayr, KA6 6DX, United Kingdom
Basingstoke and North Hampshire Hospital
Basingstoke, RG24 9NA, United Kingdom
Bedford General Hospital
Bedford, United Kingdom
Royal Bournemouth Hospital
Bournemouth, BH7 7DW, United Kingdom
Bristol Haematology & Cancer Centre
Bristol, BS2 8ED, United Kingdom
West Suffolk Hospital
Bury St Edmunds, IP33 2QZ, United Kingdom
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
Colchester General Hospital
Colchester, CO4 5JL, United Kingdom
Russells Hall Hospital
Dudley, DY1 2HQ, United Kingdom
Hinchingbrooke Hospital
Huntingdon, PE29 6NT, United Kingdom
Ipswich Hospital
Ipswich, IP4 5PD, United Kingdom
Kidderminster General Hospital
Kidderminster, DY11 6RJ, United Kingdom
University Hospital Crosshouse
Kilmarnock, KA2 0BE, United Kingdom
University College London Hospital
London, NW1 2PG, United Kingdom
Royal Free Hospital
London, NW3 2QG, United Kingdom
Mount Vernon Cancer Centre
Northwood, HA6 2RN, United Kingdom
Nottingham City Hospital
Nottingham, NG5 1PB, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
Peterborough City Hospital
Peterborough, PE3 9GZ, United Kingdom
Poole Hospital
Poole, BH15 2JB, United Kingdom
The Alexandra Hopsital
Redditch, B98 7, United Kingdom
Queen's Hospital
Romford, RM7 OAG, United Kingdom
Southampton General Hospital
Southampton, SO16 6YD, United Kingdom
Singleton Hospital
Swansea, SA2 8QA, United Kingdom
Royal Hampshire County Hospital
Winchester, SO22 5DG, United Kingdom
Worcestershire Royal Hospital
Worcester, WR5 1DD, United Kingdom
Related Publications (3)
Abraham JE, O'Connor LO, Grybowicz L, Alba KP, Dayimu A, Demiris N, Harvey C, Drewett LM, Lucey R, Fulton A, Roberts AN, Worley JR, Chhabra MA, Qian W, Brown J, Hardy R, Vallier AL, Chan S, Cidon MEU, Sherwin E, Chakrabarti A, Sadler C, Barnes J, Persic M, Smith S, Raj S, Borley A, Braybrooke JP, Staples E, Scott LC, Palmer CA, Moody M, Churn MJ, Pilger D, Zagnoli-Vieira G, Wijnhoven PWG, Mukesh MB, Roylance RR, Schouten PC, Levitt NC, McAdam K, Armstrong AC, Copson ER, McMurtry E, Galbraith S, Tischkowitz M, Provenzano E, O'Connor MJ, Earl HM; PARTNER Trial Group. Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial. Nat Commun. 2025 May 13;16(1):4269. doi: 10.1038/s41467-025-59151-0.
PMID: 40360463DERIVEDAbraham JE, Pinilla K, Dayimu A, Grybowicz L, Demiris N, Harvey C, Drewett LM, Lucey R, Fulton A, Roberts AN, Worley JR, Chhabra A, Qian W, Vallier AL, Hardy RM, Chan S, Hickish T, Tripathi D, Venkitaraman R, Persic M, Aslam S, Glassman D, Raj S, Borley A, Braybrooke JP, Sutherland S, Staples E, Scott LC, Davies M, Palmer CA, Moody M, Churn MJ, Newby JC, Mukesh MB, Chakrabarti A, Roylance RR, Schouten PC, Levitt NC, McAdam K, Armstrong AC, Copson ER, McMurtry E, Tischkowitz M, Provenzano E, Earl HM. The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer. Nature. 2024 May;629(8014):1142-1148. doi: 10.1038/s41586-024-07384-2. Epub 2024 Apr 8.
PMID: 38588696DERIVEDWoitek R, McLean MA, Ursprung S, Rueda OM, Manzano Garcia R, Locke MJ, Beer L, Baxter G, Rundo L, Provenzano E, Kaggie J, Patterson A, Frary A, Field-Rayner J, Papalouka V, Kane J, Benjamin AJV, Gill AB, Priest AN, Lewis DY, Russell R, Grimmer A, White B, Latimer-Bowman B, Patterson I, Schiller A, Carmo B, Slough R, Lanz T, Wason J, Schulte RF, Chin SF, Graves MJ, Gilbert FJ, Abraham JE, Caldas C, Brindle KM, Sala E, Gallagher FA. Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients. Cancer Res. 2021 Dec 1;81(23):6004-6017. doi: 10.1158/0008-5472.CAN-21-1499. Epub 2021 Oct 8.
PMID: 34625424DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jean Abraham
The University of Cambridge, Department of Oncology
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
July 26, 2016
First Posted
May 12, 2017
Study Start
May 1, 2016
Primary Completion
June 1, 2024
Study Completion (Estimated)
June 1, 2034
Last Updated
November 14, 2022
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF, CSR
- Time Frame
- While the trial is on-going: dependant on specific request. After the end of the trial: (as per our funding T\&Cs) data will be released into an open-source web repository.
- Access Criteria
- Formal application to the Partner TMG and Chief Investigator.
All Clinical Trial data will be considered to be shared on formal application to the Trial CI \& TMG, however data affecting or considered as having the potential to affect the integrity or the endpoints of the trial and/or other collaborations will not be shared (or until such time that they no longer are deemed to have an effect).