PARTNER: Platinum and PARP inhibitor for neoadjuvant treatment of triple-negative and/or BRCA-positive breast cancer
| ISRCTN | ISRCTN58892741 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN58892741 |
| EudraCT/CTIS number | 2015-002811-13 |
| IRAS number | 178681 |
| ClinicalTrials.gov number | NCT03150576 |
| Secondary identifying numbers | 30433, IRAS 178681 |
- Submission date
- 16/07/2018
- Registration date
- 20/11/2018
- Last edited
- 05/12/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Contact information
Dr Study Team
Scientific
Scientific
Cambridge Cancer Trials Centre (S4)
Box 279
Addenbrooke’s Hospital
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom
| Phone | None provided |
|---|---|
| cuh.partner@nhs.net |
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific 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 |
| Study acronym | PARTNER |
| Study objectives | This trial investigates whether introducing olaparib at an earlier stage of breast cancer might produce more shrinkage of the breast cancer before surgery, which may allow a better chance of avoiding mastectomy and may lead to a better chance of avoiding recurrence of the breast cancer. |
| Ethics approval(s) | North West - Haydock Research Ethics Committee, 05/01/2016, ref: 15/NW/0926 |
| Health condition(s) or problem(s) studied | Breast cancer |
| Intervention | Patients are randomised using a web-based system. Eligible patients will be randomly assigned to either the control arm (chemotherapy alone) or one of the two research arms (chemotherapy with olaparib at different timings) using minimisation method in a 1:1:1 ratio in Stage 1 and Stage 2. At the end of stage 2, one of the research treatments will be dropped using the ‘pick the winner’ method. In Stage 3, patients will be randomly assigned with a 1:1 ratio to either control or the selected research arm. Control arm: 4 cycles of: Paclitaxel 80mg/m2 Day 1, 8 & 15, every 3 weeks, Carboplatin AUC5, Day 1, every 3 weeks. Research arm 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, D-2 to D10 every 3 weeks Research arm 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, D3 to D14 every 3 weeks. 3 cycles of anthracycline-based chemotherapy. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II/III |
| Drug / device / biological / vaccine name(s) | Paclitaxel, carboplatin, olaparib |
| Primary outcome measure | 1. Safety of the addition of olaparib to three weekly carboplatin / weekly paclitaxel chemotherapy 2. 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 3. pCR at surgery after neoadjuvant treatment 4. 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 Timepoint(s): Stage I Safety, Stage II pCR, Stage III pCR |
| Secondary outcome measures | 1. pCR at surgery, assessed by central pathology review of the diagnosis and surgery slides. Time Frame: Up to 2 years after last patient randomised 2. Relapse-Free Survival (RFS), calculated from date of randomisation to date of first relapse or date of death from all causes, whichever occurs first. Time Frame: Up to 10 years after last patient is randomised 3. Breast cancer specific survival (BCSS), calculated from date of randomisation to date of death from breast cancer. Time Frame: Up to 10 years after last patient is randomised 4. 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. Time Frame: Up to 10 years after last patient is randomised 5. 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. Time Frame: Up to 10 years after last patient is randomised 6. Overall survival (OS), calculated from date of randomisation to date of death from all causes. Time Frame: Up to 10 years after last patient is randomised 7. Time to second cancer (TTSC), calculated from the date of randomisation to the date of diagnosis of second cancer. Time Frame: Up to 10 years after last patient is randomised 8. pCR in breast alone. Time Frame: Up to 2 years after last patient is randomised 9. Residual Cancer Burden (RCB) I-III will be assessed by central pathology review. Time Frame: Up to 10 years after last patient is randomised 10. Radiological response, assessed by radiological response criteria as per RECIST v1.1 after 4th and final cycles. Time Frame: Up to 2 years after last patient is randomised 11. Treatment related toxicities, assessed by CTCAE v4.03. Time Frame: Up to 10 years after last patient is randomised 12. Quality of life (sub-study). Time Frame: Up to 10 years after last patient is randomised Other pre-specified outcome measures: Discovery and validation of prognostic, pharmacogenetic and pharmacogenomic markers that can be correlated with outcomes (pCR and RFS) in patients randomised to receive olaparib compared with those who are not. Time Frame: Up to 15 years after last patient is randomised |
| Overall study start date | 07/07/2015 |
| Completion date | 30/01/2034 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 780, including a minimum of 188 patients with gBRCA breast cancer |
| Key inclusion criteria | Current inclusion criteria as of 13/01/2022: 1. Aged between 16 and 70 at time of Informed Consent 2. 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 3. Histologically confirmed invasive breast cancer 4. ER-negative, and HER2-negative breast cancer (TNBC, non-BRCA). 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 Note: mutation in BRCA1 or BRCA2 must be documented and predicted to be detrimental/lead to loss of function. 5. T1c, T2 or T3 tumours (>10 mm diameter) OR 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 >10 mm - Non-BRCA patients with multifocal disease are eligible to enter the trial provided that these foci are TNBC and one of them meets the size criteria above. If a patient is thought to have unifocal disease at diagnosis and then is later found to be multifocal they may remain within the trial as long as no new foci are HER2 positive 6. Patients with bilateral disease are eligible to enter the trial provided they are either BRCA positive or that both breast diseases are HER2 negative and one of them meets the size criteria above and is TNBC 7. 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 8. 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 9. Availability of the Tumour Infiltrating Lymphocytes score is required 10. Availability of CK5/6 and/or EGFR +/- Androgen Receptor IHC score if the patient is non-BRCA TNBC 11. Availability of slides and paraffin-embedded tissue blocks from pre-treatment core biopsy and from primary surgical resection is required 12. Women of child-bearing potential (WCBP), defined as not surgically sterilized or not post-menopausal for at least 24 consecutive months if age ≤55 years or 12 months if age >55 years, must have a negative serum pregnancy test within 14 days prior to randomisation. Once a negative pregnancy test is received the patient must be informed that they must use adequate contraception for at least 6 months after the last dose of the trial treatment. 13. 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 must use effective forms of contraception, throughout their participation in the trial and for at least 6 months after the last dose of trial treatment. Previous inclusion criteria: 1. Aged between 16 and 70 at time of Informed Consent 2. 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 3. Histologically confirmed invasive breast cancer 4. 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 Note: mutation in BRCA1 or BRCA2 must be documented and predicted to be detrimental/lead to loss of function 5. T1, T2 or T3 tumours (>10mm diameter) OR 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, see Appendix 5) 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, see Appendix 5), 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 multifocal disease are eligible to enter the trial provided that these foci are TNBC and one of them meets the size criteria above. If a patient is thought to have unifocal disease at diagnosis and then is later found to be multifocal they may remain within the trial as long as no new foci are HER2 positive 6. Patients with bilateral disease are eligible to enter the trial provided they are either BRCA positive or that both breast diseases are TNBC and one of them meets the size criteria above 7. 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 8. 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 9. Availability of the Tumour Infiltrating Lymphocytes score is required 10. Availability of CK5/6 and/or EGFR +/- Androgen Receptor IHC score if patient is TNBC 11. Availability of slides and paraffin embedded tissue blocks from pre-treatment core biopsy and from primary surgical resection is required 12. 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 pregnancy test within 14 days prior to randomisation. Once a negative pregnancy test is received the patient must be informed that they must use adequate contraception for at least 6 months after the last dose of the trial treatment 13. 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 |
| Key exclusion criteria | Current exclusion criteria as of 13/01/2022: 1. T0 tumour in absence of axillary node >10 mm 2. TNBC with a non-basal phenotype and over-expressing Androgen Receptor 3. Triple-negative subtypes such as adenoid cystic, apocrine, metaplastic, low grade adenosquamous or secretory carcinoma 4. Patients diagnosed with ipsilateral synchronous ER-positive (Allred Score >3) breast cancer tumours (known at inclusion) in absence of germline BRCA mutation 5. Previous or concomitant chemotherapy or biological agents used for the treatment of cancer in the last 5 years 6. 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. 7. Patients with myelodysplastic syndrome/acute myeloid leukaemia 8. Previous history of allogeneic marrow transplant 9. Evidence of distant metastasis apparent prior to randomisation 10. Patients with uncontrolled seizures. Pre-existing sensory or motor neuropathy of CTCAE v4.03, grade ≥2, There are some possible exceptions in cases of severe pre-existing disability. 11. Concomitant use of known potent CYP3A4 inhibitors and inducers. There is consideration for wash-out periods. 12. Pregnant or breastfeeding women 13. Not suitable for neoadjuvant chemotherapy in the opinion of the responsible clinician 14. Major surgery within 14 days prior to starting trial treatment and patients must have recovered from any effects of any major surgery 15. 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. 16. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the trial medication. This includes but is not limited to refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection 17. Known hypersensitivity to olaparib, carboplatin, paclitaxel or their excipients (including cremophor) 18. Whole blood transfusions in the last 120 days prior to blood sampling for the BRCA test as it may interfere with the results (packed red blood cells and platelet transfusions are acceptable) Previous exclusion criteria: 1. T0 tumour in absence of axillary node >10 mm 2. TNBC with a non-basal phenotype and over-expressing Androgen Receptor 3. Not suitable for neoadjuvant chemotherapy 4. Distant metastases apparent prior to randomisation 5. Prior history of invasive breast cancer within the last 5 years 6. Previous PARP inhibitor use or any previous chemotherapy or targeted agent. 7. Any previous chemotherapy or agent used for the treatment of cancer within the last 5 years |
| Date of first enrolment | 30/05/2016 |
| Date of final enrolment | 31/12/2024 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
University Hospital Crosshouse
Kilmarnock Road
Kilmarnock
KA2 0BE
United Kingdom
Kilmarnock
KA2 0BE
United Kingdom
University Hospital Ayr
Dalmellington Road
Ayr
KA6 6DX
United Kingdom
Ayr
KA6 6DX
United Kingdom
Addenbrooke’s Hospital
Hill’s Road
Cambridge
CB2 0QQ
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
Southampton
SO16 6YD
United Kingdom
West Suffolk Hospital
Hardwick Lane
Bury Saint Edmunds
IP33 2QZ
United Kingdom
Bury Saint Edmunds
IP33 2QZ
United Kingdom
Colchester General Hospital
Turner Road
Colchester
CO4 5JL
United Kingdom
Colchester
CO4 5JL
United Kingdom
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Royal Bournemouth Hospital
Castle Lane East
Bournemouth
BH7 7DW
United Kingdom
Bournemouth
BH7 7DW
United Kingdom
Peterborough City Hospital
Bretton Gate
Peterborough
PE3 9GZ
United Kingdom
Peterborough
PE3 9GZ
United Kingdom
Basingstoke and North Hampshire Hospital
Aldermaston Road
Basingstoke
RG24 9NA
United Kingdom
Basingstoke
RG24 9NA
United Kingdom
Royal Hampshire County Hospital
Romsey Road
Winchester
SO22 5DG
United Kingdom
Winchester
SO22 5DG
United Kingdom
Velindre Cancer Centre
Velindre Road
Cardiff
CF14 2TL
United Kingdom
Cardiff
CF14 2TL
United Kingdom
University College London Hospital
Euston Road
London
NW1 2PG
United Kingdom
London
NW1 2PG
United Kingdom
Bristol Haematology & Cancer Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom
Bristol
BS2 8ED
United Kingdom
Worcestershire Royal Hospital
Charles Hastings Way
Worcester
WR5 1DD
United Kingdom
Worcester
WR5 1DD
United Kingdom
Kidderminster General Hospital
Bewdley Road
Kidderminster
DY11 6RJ
United Kingdom
Kidderminster
DY11 6RJ
United Kingdom
The Alexandra Hospital
Woodrow Drive
Redditch
B98 7UB
United Kingdom
Redditch
B98 7UB
United Kingdom
Bedford General Hospital
Kempston Road
Bedford
MK42 9DJ
United Kingdom
Bedford
MK42 9DJ
United Kingdom
Churchill Hospital
Old Road
Oxford
OX3 7LE
United Kingdom
Oxford
OX3 7LE
United Kingdom
Queen’s Hospital
Rom Valley Way
Romford
RM7 OAG
United Kingdom
Romford
RM7 OAG
United Kingdom
Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom
London
NW3 2QG
United Kingdom
Russells Hall Hospital
Pensnett Road
Dudley
DY1 2HQ
United Kingdom
Dudley
DY1 2HQ
United Kingdom
Pinderfields General Hospital
Aberford Road
Wakefield
WF1 4DG
United Kingdom
Wakefield
WF1 4DG
United Kingdom
Burton Hospitals NHS Foundation Trust
Queen's Hospital
Belvedere Road
Burton-on-trent
DE13 0RB
United Kingdom
Belvedere Road
Burton-on-trent
DE13 0RB
United Kingdom
The Christie NHS Foundation Trust
550 Wilmslow Road
Withington
Manchester
M20 4BX
United Kingdom
Withington
Manchester
M20 4BX
United Kingdom
University Hospitals Dorset NHS Foundation Trust
Management Offices
Poole Hospital
Longfleet Road
Poole
BH15 2JB
United Kingdom
Poole Hospital
Longfleet Road
Poole
BH15 2JB
United Kingdom
Ipswich Hospital
Heath Road
Ipswich
IP4 5PD
United Kingdom
Ipswich
IP4 5PD
United Kingdom
Singleton Hospital
Sketty Lane
Sketty
Swansea
SA2 8QA
United Kingdom
Sketty
Swansea
SA2 8QA
United Kingdom
Hinchingbrooke Hospital
Hinchingbrooke Park
Huntingdon
PE29 6NT
United Kingdom
Huntingdon
PE29 6NT
United Kingdom
Mount Vernon Hospital
Rickmansworth Road
Northwood
HA6 2RN
United Kingdom
Northwood
HA6 2RN
United Kingdom
Sponsor information
Cambridge University Hospitals NHS Foundation Trust
Hospital/treatment centre
Hospital/treatment centre
Addenbrooke’s Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
| Phone | +44 (0)1223 217418 |
|---|---|
| research@addenbrookes.nhs.uk | |
"ROR" |
https://ror.org/04v54gj93 |
Funders
Funder type
Industry
AstraZeneca
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- AstraZeneca PLC, Pearl Therapeutics
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/01/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
05/12/2023: The study contact was updated.
20/11/2023: The contact email was updated.
14/01/2022: Publication and dissemination plan and IPD sharing statement added.
13/01/2022: The following changes were made to the trial record:
1. IRAS number added.
2. The overall trial end date was changed from 30/01/2032 to 30/01/2034.
3. The inclusion and exclusion criteria were updated.
4. The target number of participants was changed from 'Planned Sample Size: 527; UK Sample Size: 395' to 'Planned Sample Size: 780, including a minimum of 188 patients with gBRCA breast cancer'.
5. The recruitment end date was changed from 31/12/2021 to 31/12/2024.
6. Burton Hospital, The Christie NHS Foundation Trust, University Hospitals Dorset NHS Foundation Trust, Ipswich Hospital, Singleton Hospital, Hinchingbrooke Hospital, Mount Vernon Hospital were added as trial participating centres.
7. The intention to publish date was changed from 30/01/2033 to 30/01/2025.
05/03/2019: Link to plain English summary added.
23/11/2018: Internal review.
