Condition category
Cancer
Date applied
16/07/2018
Date assigned
20/11/2018
Last edited
23/11/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Anne Vallier

ORCID ID

Contact details

Cambridge Cancer Trials Centre (S4)
Box 279
Addenbrooke’s Hospital
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223348086
anne-laure.vallier@addenbrookes.nhs.uk

Additional identifiers

EudraCT number

2015-002811-13

ClinicalTrials.gov number

NCT03150576

Protocol/serial number

30433

Study information

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

Acronym

PARTNER

Study hypothesis

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

North West - Haydock Research Ethics Committee, 05/01/2016, ref: 15/NW/0926

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

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

Phase

Phase II/III

Drug names

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 trial start date

07/07/2015

Overall trial end date

30/01/2032

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 527; UK Sample Size: 395

Participant exclusion criteria

1. T0 tumour in absence of axillary node > 10mm
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

Recruitment start date

30/05/2016

Recruitment end date

31/12/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospital Crosshouse
Kilmarnock Road
Kilmarnock
KA2 0BE
United Kingdom

Trial participating centre

University Hospital Ayr
Dalmellington Road
Ayr
KA6 6DX
United Kingdom

Trial participating centre

Addenbrooke’s Hospital
Hill’s Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

West Suffolk Hospital
Hardwick Lane
Bury Saint Edmunds
IP33 2QZ
United Kingdom

Trial participating centre

Colchester General Hospital
Turner Road
Colchester
CO4 5JL
United Kingdom

Trial participating centre

Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Royal Bournemouth Hospital
Castle Lane East
Bournemouth
BH7 7DW
United Kingdom

Trial participating centre

Peterborough City Hospital
Bretton Gate
Peterborough
PE3 9GZ
United Kingdom

Trial participating centre

Basingstoke and North Hampshire Hospital
Aldermaston Road
Basingstoke
RG24 9NA
United Kingdom

Trial participating centre

Royal Hampshire County Hospital
Romsey Road
Winchester
SO22 5DG
United Kingdom

Trial participating centre

Velindre Cancer Centre
Velindre Road
Cardiff
CF14 2TL
United Kingdom

Trial participating centre

University College London Hospital
Euston Road
London
NW1 2PG
United Kingdom

Trial participating centre

Bristol Haematology & Cancer Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom

Trial participating centre

Worcestershire Royal Hospital
Charles Hastings Way
Worcester
WR5 1DD
United Kingdom

Trial participating centre

Kidderminster General Hospital
Bewdley Road
Kidderminster
DY11 6RJ
United Kingdom

Trial participating centre

The Alexandra Hospital
Woodrow Drive
Redditch
B98 7UB
United Kingdom

Trial participating centre

Bedford General Hospital
Kempston Road
Bedford
MK42 9DJ
United Kingdom

Trial participating centre

Churchill Hospital
Old Road
Oxford
OX3 7LE
United Kingdom

Trial participating centre

Queen’s Hospital
Rom Valley Way
Romford
RM7 OAG
United Kingdom

Trial participating centre

Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom

Trial participating centre

Russells Hall Hospital
Pensnett Road
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

Pinderfields General Hospital
Aberford Road
Wakefield
WF1 4DG
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust

Sponsor details

Addenbrooke’s Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 217418
research@addenbrookes.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

AstraZeneca

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

30/01/2033

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

23/11/2018: Internal review.