Breast CancerPhase 2/3PARTNERNCT03150576
Platinum and Polyadenosine 5'Diphosphoribose Polymerisation Inhibitor for Neoadjuvant Treatment of Triple Negative Breast Cancer and/or Germline BRCA Positive Breast Cancer
A Phase 2/3 study testing Olaparib and Paclitaxel and Carboplatin in people with Breast Cancer, run by Cambridge University Hospitals NHS Foundation Trust at 30 sites in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Olaparib and Paclitaxel and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 780 participants
- Where
- 30 sitesUnited Kingdom
- Study dates
- May 2016to Jun 2034
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- OR
- Germline BRCA (gBRCA) mutation positive, HER2 negative, and PgR / ER of any status.
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- 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.
- OR
- 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.
- Treatment should be commenced within 6 weeks of the diagnostic biopsy. In uncommon circumstances, where medically acceptable, treatment is permitted to start within a maximum of 9 weeks of the diagnostic biopsy.
- Availability of the Tumour Infiltrating Lymphocytes score is required.
- Availability of CK 5/6 and EGFR +/- Androgen Receptor IHC score.
- Availability of slides and paraffin embedded tissue blocks from pre-chemotherapy core biopsy and from primary surgical resection is required.
- Women of child-bearing potential (WCBP), defined as not surgically sterilized or not post-menopausal for at least 24 consecutive months if age ≤55 year or 12 months if age >55 years, must have a negative serum or urine pregnancy test within 14 days prior to randomisation.
- All WCBP and all sexually active male patients as well as their partners must be aware that they should not conceive during the treatment period and therefore should routinely use effective forms of contraception, throughout their participation in the trial and for at least 6 months after the last dose of trial treatment. Please follow the olaparib contraception guidelines.
Who cannot join
- 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.
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- 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.
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the trial medication
- Known hypersensitivity to olaparib, carboplatin, paclitaxel or their excipients (including cremophor).
- Whole blood transfusions in the last 120 days prior to blood sampling for BRCA test as it may interfere with the results (packed red blood cells and platelet transfusions are acceptable).
Trial locations and contacts
30 sites in 1 country. Contact the study team or a site near you to ask about taking part.
30 sites in 1 country
United Kingdom30 sites, 30 recruiting
- Recruiting
University Hospital Ayr
Ayr, KA6 6DX
First Contact, 01563 825858
Lucy Scott
- Recruiting
Basingstoke and North Hampshire Hospital
Basingstoke, RG24 9NA
First Contact, 01256 473202
Sanjay Raj
- Recruiting
Bedford General Hospital
Bedford
First Contact, 01234 795924
Shahzeena Aslam
- Recruiting
Royal Bournemouth Hospital
Bournemouth, BH7 7DW
First Contact, 01202704773
Maria Cidon
- Recruiting
Bristol Haematology & Cancer Centre
Bristol, BS2 8ED
First Contact, 0117 342 6736
Jeremy Braybrooke
- Recruiting
Queen's Hospital
Burton-on-Trent, Derby, De13 ORB
First Contact, 01283 511511
Mojca Persic
- Recruiting
West Suffolk Hospital
Bury St Edmunds, IP33 2QZ
First Contact, 01284 712763
Margaret Moody
- Recruiting
Cambridge University Hospitals NHS Foundation Trust & the University of Cambridge
Cambridge, Cambridgeshire, CB2 0QQ
CCTC Cambridge Cancer Trials Centre, +44(0) 1223 348071
Jean Abraham
- Recruiting
Velindre Cancer Centre
Cardiff, CF14 2TL
First Contact, 02920615888
Annabel Borley
- Recruiting
Colchester General Hospital
Colchester, CO4 5JL
First Contact, 01206 745 355
MB Mukesh
- Recruiting
Russells Hall Hospital
Dudley, DY1 2HQ
First Contact, 01384 456111
Devanshi Tripathi
- Recruiting
Hinchingbrooke Hospital
Huntingdon, PE29 6NT
Cheryl Palmer
- Recruiting
Ipswich Hospital
Ipswich, IP4 5PD
Ramachandran Venkitaraman
- Recruiting
Kidderminster General Hospital
Kidderminster, DY11 6RJ
First Contact, 01562 513275
Mark Churn
- Recruiting
University Hospital Crosshouse
Kilmarnock, KA2 0BE
First Contact, 01563 825858
Lucy Scott
- Recruiting
University College London Hospital
London, NW1 2PG
First Contact, 02034474741
Rebecca Roylance
- Recruiting
Royal Free Hospital
London, NW3 2QG
First Contact, 0207 794 0500
Jackie Newby
- Recruiting
The Christie
Manchester, Lancs, M20 4GJ
First Contact, 0161 446 3000
Anne Armstrong
- Recruiting
Mount Vernon Cancer Centre
Northwood, HA6 2RN
Stephanie Sutherland
- Recruiting
Nottingham City Hospital
Nottingham, NG5 1PB
First Contact, 0115 969 1169
Stephen Chan
- Recruiting
Churchill Hospital
Oxford, OX3 7LE
First Contact, 01865 572025
Nicola Levitt
- Recruiting
Peterborough City Hospital
Peterborough, PE3 9GZ
First Contact, 01733 673167
Karen McAdam
- Recruiting
Poole Hospital
Poole, BH15 2JB
Amit Chakrabarti
- Recruiting
The Alexandra Hopsital
Redditch, B98 7
First Contact, 01527 505788
Mark Churn
- Recruiting
Queen's Hospital
Romford, RM7 OAG
First Contact, 01708 435297
Emma Staples
- Recruiting
Southampton General Hospital
Southampton, SO16 6YD
First Contact, 02381 204618
Ellen Copson
- Recruiting
Singleton Hospital
Swansea, SA2 8QA
David Davies
- Recruiting
Pinderfields General Hospital
Wakefield, Yorkshire, WF1 4DG
First Contact, 01924 542486
Sreedevi Kumar
- Recruiting
Royal Hampshire County Hospital
Winchester, SO22 5DG
First Contact, 01962 824634
Sanjay Raj
- Recruiting
Worcestershire Royal Hospital
Worcester, WR5 1DD
First Contact, 01905 733194
Mark Churn
About this study
Official title: 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.
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).
Read the detailed description
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.
Disease under investigation: Breast Cancer
Purpose of clinical trial: To establish if the addition of olaparib to neoadjuvant platinum-based chemotherapy for Triple Negative Breast Cancer (TNBC) and/or germline BRCA (gBRCA) breast cancer is safe and improves efficacy.
Trial Design: Open label, randomised, 3-stage Phase II/III
Sample Size: Minimum of 780 patients (including at least 220 gBRCA patients equally allocated to the control and the selected research arm).
Non Investigational Medicinal Products: Prophylactic granulocyte-colony stimulating factor (G-CSF) to be given as per local practice and 3 cycles of anthracyclines as per local practice.
Treatment period: A minimum of 21 weeks of chemotherapy followed by surgery.
Procedures: Screening \& enrolment
Eligible patients with early breast cancer will be registered and consented for screening:
BRCA mutation test Tumour Infiltrating Lymphocytes(TILs) score Cytokeratin 5/6 (CK5/6), Epidermal Growth Factor Receptor (EGFR) +/-, Androgen Receptor (AR) status by Immunohistochemistry (IHC).
Standard assessment prior to chemotherapy Standard staging to exclude metastatic disease. When eligibility is confirmed, patients will be randomised via a web-based central system which will allocate each patient a unique randomisation number associated with one of the treatment arms.
PARTNERing Pathway - For those patients who still have residual disease after receiving neoadjuvant chemotherapy +/- olaparib there is the opportunity to be screened to a sub-study to receive a further two cycles of chemotherapy consisting of Duralumab and AZD6738.
End of Trial: For patients, the end of trial is after the last follow-up visit or contact with the research team planned 10 years after surgery.
Procedures for safety monitoring during trial: Pharmacovigilance will be performed by the PARTNER Trial Office. Also, the Trial Management Group and the Independent Data and Safety Monitoring Committee will regularly review the patient safety data.
Criteria for discontinuation of trial treatment on safety grounds:
Severe toxicity or inter-current illness, requiring cessation in the judgement of patient's clinician.
Patient within 4 weeks has not recovered from toxicity to an extent that allows further treatment.
Patient unable to comply with trial procedures. Disease progression while on trial treatment. Patient becomes pregnant.
- Conditions
- Breast Cancer
- Being tested
- Olaparib, Paclitaxel and Carboplatin
- Keywords
- Triple negative breast cancer, germline BRCA, platinum and PARP inhibitor, neoadjuvant chemotherapy, olaparib
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Also called Lynparza
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 and CarboplatinDrug
Also called Taxol and Paraplatin
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.
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | 4 cycles of: Paclitaxel 80mg/m2 Day 1, 8 \& 15, every 3 weeks, Carboplatin area under the curve (AUC) 5 Day 1, every 3 weeks Receives: Drug: Paclitaxel and Carboplatin |
| Research 1 | Experimental | 4 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 Receives: Drug: Olaparib; Drug: Paclitaxel and Carboplatin |
| Research 2 | Experimental | 4 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 Receives: Drug: Olaparib; Drug: Paclitaxel and Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 5.5 years - October 2021 approx.
Secondary outcomes (13)
pCR at surgery - assessed by review of histopathology slides
pCR at surgery assessed by central pathology review of the diagnosis and surgery slides.
Measured: Up to 2 years after last patient randomised
PARTNERing Pathway
For those patients who still have residual disease after receiving neoadjuvant chemotherapy there is the opportunity to receive a further two cycles of Duralumab and AZD6738. Durvalumab I.V will be administered on cycle 1, day 1 and cycle 2, day 1. AZD6738 will be self administered by patients by mouth twice a day for 7 days beginning on cycle 1, day 22 and cycle 2, day 22.
Measured: 2 cycles (each lasting 28 days)
Relapse-Free Survival (RFS)
Relapse Free Survival (RFS), calculated from date of randomisation to date of first relapse or date of death from all causes, whichever occurs first.
Measured: Up to 10 years after last patient is randomised
Breast cancer specific survival (BCSS)
Breast cancer specific survival (BCSS), calculated from date of randomisation to date of death from breast cancer.
Measured: Up to 10 years after last patient is randomised
Distant disease-free survival
Distant disease-free survival, calculated from date of randomisation to date of the first distant disease relapse or date of death from all causes, whichever occurs first.
Measured: Up to 10 years after last patient is randomised
Local recurrence-free survival
Local recurrence-free survival, calculated from date of randomisation to date of the first local recurrence or date of death from all causes, whichever occurs first.
Measured: Up to 10 years after last patient is randomised
Overall survival (OS)
Overall survival (OS), calculated from date of randomisation to date of death from all causes.
Measured: Up to 10 years after last patient is randomised
Time to second cancer (TTSC)
Time to second cancer (TTSC), calculated from the date of randomisation to the date of diagnosis of second cancer.
Measured: Up to 10 years after last patient is randomised
pCR in breast alone
pCR in breast alone
Measured: Up to 2 years after last patient is randomised
Residual Cancer Burden (RCB)
Residual Cancer Burden (RCB) I-III will be assessed by central pathology review.
Measured: Up to 10 years after last patient is randomised
Radiological response - as assessed by radiological response criteria as per RECIST v1.1
Radiological response after 4th and final cycles
Measured: Up to 2 years after last patient is randomised
Treatment related toxicities - as assessed by CTCAE v4.03
Treatment related toxicities
Measured: Up to 10 years after last patient is randomised
Quality of Life Questionnaire
Quality of Life (sub-study). Questionnaire to be completed by patient prior to start of treatment, following cycle 4 and cycle 7, following surgery and then annually for two years to document long-term effects on quality of life.
Measured: Up to 10 years after last patient is randomised
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study startMay 2016
- Primary completionJun 2024 (estimated)
- Study completionJun 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 780 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Cancer Research UK
- Responsible party
- Principal investigator, Prof. Jean Abraham, University of Cambridge
- Investigators
- Jean Abraham, Principal investigator, The University of Cambridge, Department of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03150576
- Sponsor's protocol ID
- PARTNER
- Acronym
- PARTNER
- Status last verified
- Nov 2022
- First submitted
- 26 Jul 2016
- Last updated
- 14 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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).
Publications
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.
PubMed 40360463Abraham 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.
PubMed 38588696Woitek 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.
PubMed 34625424