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Looking for participantsPhase2/Phase3

Platinum and Polyadenosine 5'Diphosphoribose Polymerisation Inhibitor for Neoadjuvant Treatment of Triple Negative Breast Cancer and/or Germline BRCA Positive Breast Cancer

Sponsor: Cambridge University Hospitals NHS Foundation Trust

NCT ID: NCT03150576

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
Olaparib (drug), Paclitaxel and Carboplatin (drug)
How long the study runs
Study runs about 217 months (dates as stated)
About the drug or intervention
Olaparib — drug: Patients will self-administer Olaparib by mouth. · Paclitaxel and Carboplatin — drug: Paclitaxel I.V.
Patient visit burden
Not specified by the sponsor

In plain English

This trial, run by Cambridge University Hospitals NHS Foundation Trust, is looking at breast cancer treatment before surgery (called neoadjuvant treatment). It involves people with triple negative breast cancer, or breast cancer linked to a faulty BRCA gene passed down in families. The trial uses a platinum chemotherapy drug together with a drug called a polyadenosine 5'diphosphoribose polymerisation inhibitor (a type of PARP inhibitor).

Who can take part

  • Aged between 16 and 70
  • Have invasive breast cancer confirmed by laboratory tests
  • Triple negative breast cancer (negative for ER and HER2, with any PR status but it must be scored), OR a faulty BRCA gene inherited from a parent (germline BRCA), with HER2-negative cancer and any ER or PR status
  • Tumour is T1, T2 or T3, or is a T4 tumour (growing into the chest wall or skin), or inflammatory cancer, or other locally advanced disease such as cancer in large or fixed lymph nodes under the arm or near the collarbone, or a multifocal tumour with at least one tumour larger than 10mm
  • Cancer in both breasts is allowed if both meet the criteria
  • Fit enough for the chemotherapy, with good bone marrow, liver and kidney function, and an activity level (performance status) of 0 or 1
  • Treatment starts within 6 weeks of the diagnostic biopsy (up to 9 weeks in some cases if medically acceptable)
  • Tests done on the tumour sample are available, including the tumour infiltrating lymphocytes score and CK 5/6 and EGFR (and possibly androgen receptor) scores, plus stored tissue samples from the biopsy and later surgery
  • Not pregnant or breastfeeding, and willing to use effective contraception during the trial and for at least 6 months after the last dose

Who may not be able to

  • No tumour found in the breast and no enlarged lymph node over 10mm
  • Triple negative breast cancer that strongly expresses the androgen receptor (a non-basal type)
  • Chemotherapy or biological cancer treatment in the last 5 years
  • Any other cancer in the last 5 years (with some exceptions, such as treated skin cancer, treated early cervical cancer, DCIS, certain treated endometrial cancer, or other cancers cured at least 5 years ago)
  • Myelodysplastic syndrome or acute myeloid leukaemia
  • Signs the cancer has already spread to other parts of the body before joining the trial
  • Uncontrolled seizures
  • Existing nerve damage (numbness, tingling or weakness) of grade 2 or worse
  • Taking certain medicines known as strong CYP3A4 inhibitors or inducers
  • Pregnant or breastfeeding
  • Not suitable for chemotherapy before surgery, in the doctor's opinion
  • Major surgery within 14 days of starting, or not yet recovered from surgery
  • Severe or uncontrolled illness that would prevent finishing treatment or follow-up, such as serious heart disease, a recent heart attack (within 12 months), or active infection including hepatitis B, hepatitis C or HIV
  • A heart tracing (ECG) showing a long QTc (over 470 milliseconds) on two or more readings in 24 hours, or a family history of long QT syndrome
  • Unable to swallow tablets, or a gut problem that might stop the medicine being absorbed
  • Allergic reaction to olaparib, carboplatin, paclitaxel or their ingredients (including cremophor)
  • A whole blood transfusion in the last 120 days before the BRCA blood test (packed red cells and platelet transfusions are acceptable)

What taking part involves

  • • Treatment before surgery (neoadjuvant treatment) with a platinum chemotherapy drug and a PARP inhibitor
  • • The drugs named in the trial include olaparib, carboplatin and paclitaxel

Time commitment: Not stated — ask the trial team

Plain-English summary (AI-generated) from registry data. Not eligibility advice — only the trial team can confirm whether you can take part. Use the eligibility checker to see how your health profile matches this trial.

Type of study
Testing a treatment
Ages
16 Years to 70 Years
Who
All
Number of participants
780
Started
2016-05
Last checked
2022-11

Plain English Summary

What is this study?

  • • Testing a new treatment for breast cancer
  • • Phase2/Phase3 - 780 participants
  • • 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)

Who can take part?

  • • Ages 16 Years to 70 Years
  • • Diagnosed with breast cancer

Where?

  • • Cambridge - Cambridge University Hospitals NHS Foundation Trust & the University of Cambridge
  • • Burton-on-Trent - Queen's Hospital
  • • Manchester - The Christie
  • • Wakefield - Pinderfields General Hospital
  • • +26 more UK sites

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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).

More detail

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 780 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. PARTNERing Pathway - For those patients who still have residual disease after receiving neoadjuvant chemotherapy +/- olaparib there is the opportunity to be screened to a sub-study to receive a further two cycles of chemotherapy consisting of Duralumab and AZD6738. 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.

Breast Cancer

How this trial compares with your answers

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What we know so far

Condition· Matched your search
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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 16 Years - 70 Years
  • Who can join: All genders
  • How fit you need to be: ECOG 0 or better

Biomarkers mentioned

ERHER2PRmutation positiveHER2 negativeEGFRhave a negative

Treatment history

Treatments you must have had:

  • ✓ a negative serum or urine pregnancy test within 14 days

What the study is looking for

  • ✓Aged between 16 and 70.
  • ✓Written agreement to take part, willing and able to comply with the Protocol for the duration of the trial including...
  • ✓confirmed by a biopsy invasive breast cancer.
  • ✓ER-negative\*, and HER2-negative\*\* breast cancer (TNBC). Patients will be eligible with any PR status but PR...
  • ✓Germline BRCA (gBRCA) mutation positive, HER2 negative, and PgR / ER of any status.

Who cannot take part

  • ✗T0 tumour in absence of axillary node \>10mm.
  • ✗TNBC with a non-basal phenotype which strongly expresses Androgen Receptor.
  • ✗Previous or concomitant drug treatment or biological agents used for the treatment of cancer in the last 5 years.
  • ✗Patients with myelodysplastic syndrome/acute myeloid leukaemia.
  • ✗Evidence of distant metastasis apparent prior to randomisation.
See the full criteria
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 0, 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).

Where Is This Study? (30 UK sites)

Cambridge University Hospitals NHS Foundation Trust & the University of Cambridge

Cambridge CB2 0QQ, United Kingdom

Recruiting
Site contact (verified)
Jean AbrahamPrincipal Investigator
CCTC Cambridge Cancer Trials Centre+44(0) 1223 348071

Queen's Hospital

Burton-on-Trent De13 ORB, United Kingdom

Recruiting
Site contact (verified)
Mojca PersicPrincipal Investigator
First Contact01283 511511

The Christie

Manchester M20 4GJ, United Kingdom

Recruiting
Site contact (verified)
Anne ArmstrongPrincipal Investigator
First Contact0161 446 3000

Pinderfields General Hospital

Wakefield WF1 4DG, United Kingdom

Recruiting
Site contact (verified)
Sreedevi KumarPrincipal Investigator
First Contact01924 542486

University Hospital Ayr

Ayr KA6 6DX, United Kingdom

Recruiting
Site contact (verified)
Lucy ScottPrincipal Investigator
First Contact01563 825858

Basingstoke and North Hampshire Hospital

Basingstoke RG24 9NA, United Kingdom

Recruiting
Site contact (verified)
Sanjay RajPrincipal Investigator
First Contact01256 473202

Bedford General Hospital

Bedford, United Kingdom

Recruiting
Site contact (verified)
Shahzeena AslamPrincipal Investigator
First Contact01234 795924

Royal Bournemouth Hospital

Bournemouth BH7 7DW, United Kingdom

Recruiting
Site contact (verified)
Maria CidonPrincipal Investigator
First Contact01202704773

Bristol Haematology & Cancer Centre

Bristol BS2 8ED, United Kingdom

Recruiting
Site contact (verified)
Jeremy BraybrookePrincipal Investigator
First Contact0117 342 6736

West Suffolk Hospital

Bury St Edmunds IP33 2QZ, United Kingdom

Recruiting
Site contact (verified)
Margaret MoodyPrincipal Investigator
First Contact01284 712763

Velindre Cancer Centre

Cardiff CF14 2TL, United Kingdom

Recruiting
Site contact (verified)
Annabel BorleyPrincipal Investigator
First Contact02920615888

Colchester General Hospital

Colchester CO4 5JL, United Kingdom

Recruiting
Site contact (verified)
MB MukeshPrincipal Investigator
First Contact01206 745 355

Russells Hall Hospital

Dudley DY1 2HQ, United Kingdom

Recruiting
Site contact (verified)
Devanshi TripathiPrincipal Investigator
First Contact01384 456111

Hinchingbrooke Hospital

Huntingdon PE29 6NT, United Kingdom

Recruiting
Site contact (verified)
Cheryl PalmerPrincipal Investigator

Ipswich Hospital

Ipswich IP4 5PD, United Kingdom

Recruiting
Site contact (verified)
Ramachandran VenkitaramanPrincipal Investigator

Kidderminster General Hospital

Kidderminster DY11 6RJ, United Kingdom

Recruiting
Site contact (verified)
Mark ChurnPrincipal Investigator
First Contact01562 513275

University Hospital Crosshouse

Kilmarnock KA2 0BE, United Kingdom

Recruiting
Site contact (verified)
Lucy ScottPrincipal Investigator
First Contact01563 825858

University College London Hospital

London NW1 2PG, United Kingdom

Recruiting
Site contact (verified)
Rebecca RoylancePrincipal Investigator
First Contact02034474741

Royal Free Hospital

London NW3 2QG, United Kingdom

Recruiting
Site contact (verified)
Jackie NewbyPrincipal Investigator
First Contact0207 794 0500

Mount Vernon Cancer Centre

Northwood HA6 2RN, United Kingdom

Recruiting
Site contact (verified)
Stephanie SutherlandPrincipal Investigator

Nottingham City Hospital

Nottingham NG5 1PB, United Kingdom

Recruiting
Site contact (verified)
Stephen ChanPrincipal Investigator
First Contact0115 969 1169

Churchill Hospital

Oxford OX3 7LE, United Kingdom

Recruiting
Site contact (verified)
Nicola LevittPrincipal Investigator
First Contact01865 572025

Peterborough City Hospital

Peterborough PE3 9GZ, United Kingdom

Recruiting
Site contact (verified)
Karen McAdamPrincipal Investigator
First Contact01733 673167

Poole Hospital

Poole BH15 2JB, United Kingdom

Recruiting
Site contact (verified)
Amit ChakrabartiPrincipal Investigator

The Alexandra Hopsital

Redditch B98 7, United Kingdom

Recruiting
Site contact (verified)
Mark ChurnPrincipal Investigator
First Contact01527 505788

Queen's Hospital

Romford RM7 OAG, United Kingdom

Recruiting
Site contact (verified)
Emma StaplesPrincipal Investigator
First Contact01708 435297

Southampton General Hospital

Southampton SO16 6YD, United Kingdom

Recruiting
Site contact (verified)
Ellen CopsonPrincipal Investigator
First Contact02381 204618

Singleton Hospital

Swansea SA2 8QA, United Kingdom

Recruiting
Site contact (verified)
David DaviesPrincipal Investigator

Royal Hampshire County Hospital

Winchester SO22 5DG, United Kingdom

Recruiting
Site contact (verified)
Sanjay RajPrincipal Investigator
First Contact01962 824634

Worcestershire Royal Hospital

Worcester WR5 1DD, United Kingdom

Recruiting
Site contact (verified)
Mark ChurnPrincipal Investigator
First Contact01905 733194

How to Get in Touch

CCTC A Cambridge Cancer Trials Centre

Sponsor contact

CONTACT

+44 (0)1223 348071 cuh.partner@nhs.net
Data sourced from ClinicalTrials.gov · Last verified: 2022-11