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

  • STATUS
    Recruiting
  • End date
    Jan 21, 2032
  • participants needed
    527
  • sponsor
    Cambridge University Hospitals NHS Foundation Trust
Updated on 21 January 2021
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, Breast Cancer Diagnosis, breast carcinoma, cancer, breast
Treatment olaparib, Paclitaxel and Carboplatin
Clinical Study IdentifierNCT03150576
SponsorCambridge University Hospitals NHS Foundation Trust
Last Modified on21 January 2021

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)
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note