PARTNER: Platinum and PARP inhibitor for neoadjuvant treatment of triple-negative and/or BRCA-positive breast cancer
- Conditions
- Breast cancerCancerMalignant neoplasm of breast
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 780
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 Inf
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Safety of the addition of olaparib to three weekly carboplatin / weekly paclitaxel chemotherapy<br>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<br>3. pCR at surgery after neoadjuvant treatment<br>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<br>Timepoint(s): Stage I Safety, Stage II pCR, Stage III pCR
- Secondary Outcome Measures
Name Time Method