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TNBC - Triple-Negative Breast CancerPhase 2NCT05209529

Chemo-free BRCA-targeted Neoadjuvant Strategy

A Phase 2 study testing olaparib and Durvalumab in people with TNBC - Triple-Negative Breast Cancer and BRCA1 Mutation, run by European Organisation for Research and Treatment of Cancer - EORTC.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a multicenter randomized phase ll clinical trial to evaluate the pathological complete response (pCR) in the tumour burden (primary and lymph nodes) with olaparib alone or in the olaparib and durvalumab arm in TNBC patients candidate for neoadjuvant strategy showing a t/gBRCAmut or BRCAness/HRD profile. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
olaparib and Durvalumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
1 Feb 2024to 18 Jul 2030
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed, invasive TNBC, defined as:
  • ER and PR negative (not eligible for endocrine therapy) defined as immunohistochemistry (IHC) nuclear staining ≤ 10% AND
  • HER2 negative (not eligible for anti-HER2 therapy):
  • Early-stage disease, defined as cT1c-T2, N0-N1, M0
  • Medically fit for a neoadjuvant strategy and for radical surgery as by the investigator's decision
  • No prior systemic therapy nor definitive surgery for BC
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  • Age ≥18 years
  • Women and men can be included
  • ECOG performance status (PS) 0-1
  • Deleterious germline or somatic mutation in BRCA 1 and/or BRCA 2 or homologue repair deficiency (HRD) status as determined by central testing.
  • Tumour tissue available from primary tumour (fine needle aspiration cytology or lymph node metastasis tissue are not acceptable).
  • Normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
  • Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelet count ≥ 100 x 109/L
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN
  • Total bilirubin ≤ 1.5 x ULN (exception: higher bilirubin in patients with confirmed Gilbert's syndrome are allowed according to the investigator's decision)
  • Creatinine clearance estimated of ≥ 51 mL/min/1.73m2 using the MDRD equation
  • Body weight >30 kg
  • Participation in translational research is mandatory
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test in the screening period and confirmed prior to treatment on day 1.
  • Female patients of childbearing/reproductive potential must use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 3 months after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Such methods include:
  • Intrauterine device (IUD)
  • Intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Vasectomized partner
  • Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
  • Male patients must use a condom during treatment and for 3 months after the last dose of study treatment when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception (see above) if they are of childbearing potential.
  • Female subjects who are breast feeding must discontinue nursing prior to the first dose of study treatment and until 3 months after the last study treatment.
  • Registration to a National Health Care System

Who cannot join

  • Previous treatment with a PARPi
  • Previous treatment with an anti-PD-1/PD-L1, anti-PD-L2 or anti-CTLA-4 antibody
  • Evidence of macroscopic distant metastases, investigated according to local institutional guidelines
  • Patients who underwent sentinel node biopsy before neoadjuvant therapy
  • History of previous invasive BC
  • Bilateral and/or multifocal and/or multicentric BC
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  • Malabsorption syndrome or other chronic condition that would significantly interfere with enteral absorption
  • History of allogenic transplantation of bone marrow or an organ.
  • History of another primary malignancy.
  • Myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of such.
  • Congenital long QT syndrome.
  • History of active primary immunodeficiency
  • Inability to swallow and/or retain oral tablets
  • Blood transfusion within 28 days
  • History of human immunodeficiency virus (HIV) (positive HIV 1/2-antibodies)
  • Active Hepatitis B or Hepatitis C
  • Active bacterial, viral, or fungal infection requiring systemic therapy
  • History of active tuberculosis (TB, Bacillus Tuberculosis)
  • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, interstitial lung disease or evidence of active pneumonitis on screening (TAP-CT-scan)
  • History of aortic disease (aneurysm or dissection)
  • History of myasthenia gravis
  • Mean QT interval corrected for heart rate (QTc) ≥ 500ms using Fridericia's Correction
  • Uncontrolled intercurrent illness
  • Psychiatric illness/social situations or addiction (chronic alcoholism or drug addiction) that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  • Any other serious or uncontrolled illness or abnormality that, in the judgment of the investigator, limits compliance with study requirement, substantially increases risk of incurring AEs or compromises the ability to give written informed consent.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment.
  • Any concurrent systemic chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
  • Any unresolved toxicity (Common Terminology Criteria for Adverse Event (CTCAE) grade ≥ 2) caused by previous cancer therapy, excluding alopecia, vitiligo.
  • Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with olaparib and/or durvalumab may be included only after consultation with the study physician.
  • Concomitant use of strong CYP3A inhibitors.The required washout period prior to starting study treatment (olaparib) is 2 weeks.
  • Concomitant use of strong CYP3A inducers. The required washout period prior to starting study treatment (olaparib) is 5 weeks for phenobarbital and 3 weeks for other agents.
  • Major surgery within 4 weeks prior to the first dose of study treatment. Patients must have recovered from the surgical procedure. Implanted port placement is not considered as a major surgery.
  • Known allergy or hypersensitivity to olaparib or durvalumab, or to any excipient.
  • Contraindication to MRI or to the contrast medium used for MRI (gadolinium).
  • Participation in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
  • Female patients who are pregnant or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 3 months after the last dose of study treatment.

About this study

Official title: Neoadjuvant Olaparib and Durvalumab for Patients With BRCA-associated Triple Negative Breast Cancer

This is a multicenter randomized phase ll clinical trial to evaluate the pathological complete response (pCR) in the tumour burden (primary and lymph nodes) with olaparib alone or in the olaparib and durvalumab arm in TNBC patients candidate for neoadjuvant strategy showing a t/gBRCAmut or BRCAness/HRD profile.

Read the detailed description

Eligible patients will be registered for central testing of BRCA mutatinal status and HRD/BRCAness profile with central review of ER, PgR, TILs and PD-L1.

Eligible patients will be randomly assigned to either olparib or olaparib and durvalumab (=neoadjuvant treatment) in a 1:1 ratio. The treatment duration in both arms will last 16 weeks and both treatments are considered as experimental treatments in this study.

After completion of neoadjuvant systemic treatment, patients will undergo surgery and followed-up for 2 years after investigational drug discontinuation. After surgery, adjuvant treatment will be left at the investigator's decision.

Being tested
olaparib, Durvalumab
Keywords
Olaparib, Durvalumab, PARPi
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT05209529
Study groupRoleWhat they receive
OlaparibExperimentalOlaparib treatment for a total of 16 weeks
Receives: Drug: olaparib
Olaparib and durvalumabExperimentalOlaparib and durvalumab treatment for a total of 16 weeks
Receives: Drug: olaparib; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. rate of pathological complete response (pCR) at the time of surgery

    pCR is defined as the absence of invasive residual disease in the breast and in the axillary lymph nodes (ypT0/is ypN0).

    Measured: 5 years from first patient in

Secondary outcomes (9)

  1. 2-year overall survival (OS) rate

    OS is defined as date of randomization to the date of death, whatever comes first

    Measured: 7.5 years from first patient in

  2. Other pathological response

    Residual cancer burden score (RCB), defined on the specimen collected at the time of surgery

    Measured: 7.5 years from first patient in

  3. Probability of being event-free at 2 years

    events considered being disease progression on neoadjuvant therapy, any event precluding surgery, locoregional recurrence, distant recurrence, second primary invasive cancer (breast and non-breast origin) and death from any cause

    Measured: 7.5 years from first patient in

  4. Surgery rate

    Measured: 7.5 years from first patient in

  5. Breast conservation rate

    Measured: 7.5 years from first patient in

  6. Treatment response rate according to RECIST v1.1

    Measured: 7.5 years from first patient in

  7. Safety

    Rate of Adverse events not related directly with the surgical procedure (NCI-CTCAE Version 5.0) Rate of Post-operative complications (Clavien-Dindo Classification of Surgical Complications)

    Measured: 7.5 years from first patient in

  8. Global health status/QoL score

    score according to EORTC QLQ-C30 questionnaire

    Measured: 7.5 years from first patient in

  9. Score on the Systemic side effects scale

    according to the modified QLQ-BR45 (IL170) questionnaire

    Measured: 7.5 years from first patient in

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2022
  2. Study start1 Feb 2024 (estimated)
  3. Primary completion6 Sep 2028 (estimated)
  4. Study completion18 Jul 2030 (estimated)

Why it stopped: Withdrawn interest from grant provider

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Eligible patients after central screening are randomized to olaparib vs olaparib and durvalumab
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05209529
Sponsor's protocol ID
EORTC-1984-BCG
Other IDs
2022-003594-33
Status last verified
Feb 2024
First submitted
12 Jan 2022
Last updated
23 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing olaparib and Durvalumab in people with TNBC - Triple-Negative Breast Cancer and BRCA1 Mutation, run by European Organisation for Research and Treatment of Cancer - EORTC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

rate of pathological complete response (pCR) at the time of surgery (time frame: 5 years from first patient in). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05209529.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2024.

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