Platinum and Polyadenosine 5'Diphosphoribose Polymerisation (PARP) Inhibitor for Neoadjuvant Treatment of Triple Negative Breast Cancer (TNBC) and/or Germline BRCA (gBRCA) Positive Breast Cancer (PARTNER)

STATUS

Recruiting
End date

Jan 21, 2032
participants needed

527
sponsor

Cambridge University Hospitals NHS Foundation Trust

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Updated on 29 January 2022

See if I qualify

paclitaxel

carcinoma

carboplatin

HER2

EGFR

adjuvant therapy

triple negative breast cancer

erbb2

invasive breast cancer

core needle biopsy

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).

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 527 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.

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.

Details

Condition	Breast Cancer
Treatment	olaparib, Paclitaxel and Carboplatin
Clinical Study Identifier	NCT03150576
Sponsor	Cambridge University Hospitals NHS Foundation Trust
Last Modified on	29 January 2022

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	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
	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
	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
	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
	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)

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Platinum and Polyadenosine 5'Diphosphoribose Polymerisation (PARP) Inhibitor for Neoadjuvant Treatment of Triple Negative Breast Cancer (TNBC) and/or Germline BRCA (gBRCA) Positive Breast Cancer (PARTNER)