Platinum and Polyadenosine 5'Diphosphoribose Polymerisation Inhibitor for Neoadjuvant Treatment of Triple Negative Breast Cancer and/or Germline BRCA Positive Breast Cancer
NCT ID: NCT03150576
Last Updated: 2022-11-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2/PHASE3
780 participants
INTERVENTIONAL
2016-05-31
2034-06-30
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Control
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
Paclitaxel and Carboplatin
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.
Research 1
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
Olaparib
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 Carboplatin
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.
Research 2
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
Olaparib
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 Carboplatin
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.
Interventions
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Olaparib
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 Carboplatin
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
* 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.
Exclusion Criteria
* 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.
* 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).
16 Years
70 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
Cancer Research UK
OTHER
Cambridge University Hospitals NHS Foundation Trust
OTHER
Responsible Party
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Prof. Jean Abraham
Professor
Principal Investigators
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Jean Abraham
Role: PRINCIPAL_INVESTIGATOR
The University of Cambridge, Department of Oncology
Locations
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Cambridge University Hospitals NHS Foundation Trust & the University of Cambridge
Cambridge, Cambridgeshire, United Kingdom
Queen's Hospital
Burton-on-Trent, Derby, United Kingdom
The Christie
Manchester, Lancs, United Kingdom
Pinderfields General Hospital
Wakefield, Yorkshire, United Kingdom
University Hospital Ayr
Ayr, , United Kingdom
Basingstoke and North Hampshire Hospital
Basingstoke, , United Kingdom
Bedford General Hospital
Bedford, , United Kingdom
Royal Bournemouth Hospital
Bournemouth, , United Kingdom
Bristol Haematology & Cancer Centre
Bristol, , United Kingdom
West Suffolk Hospital
Bury St Edmunds, , United Kingdom
Velindre Cancer Centre
Cardiff, , United Kingdom
Colchester General Hospital
Colchester, , United Kingdom
Russells Hall Hospital
Dudley, , United Kingdom
Hinchingbrooke Hospital
Huntingdon, , United Kingdom
Ipswich Hospital
Ipswich, , United Kingdom
Kidderminster General Hospital
Kidderminster, , United Kingdom
University Hospital Crosshouse
Kilmarnock, , United Kingdom
University College London Hospital
London, , United Kingdom
Royal Free Hospital
London, , United Kingdom
Mount Vernon Cancer Centre
Northwood, , United Kingdom
Nottingham City Hospital
Nottingham, , United Kingdom
Churchill Hospital
Oxford, , United Kingdom
Peterborough City Hospital
Peterborough, , United Kingdom
Poole Hospital
Poole, , United Kingdom
The Alexandra Hopsital
Redditch, , United Kingdom
Queen's Hospital
Romford, , United Kingdom
Southampton General Hospital
Southampton, , United Kingdom
Singleton Hospital
Swansea, , United Kingdom
Royal Hampshire County Hospital
Winchester, , United Kingdom
Worcestershire Royal Hospital
Worcester, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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CCTC Cambridge Cancer Trials Centre
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References
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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.
Abraham 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.
Woitek 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.
Other Identifiers
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PARTNER
Identifier Type: -
Identifier Source: org_study_id
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