Chemo-free BRCA-targeted Neoadjuvant Strategy

NCT05209529 | Withdrawn Phase 2 DMC

• 2 other identifiers: EORTC-1984-BCG2022-003594-33
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

TNBC - Triple-Negative Breast Cancer; BRCA1 Mutation; BRCA2 Mutation

Keywords

Olaparib; Durvalumab; PARPi

Outcome Measures

Primary Outcomes (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).

  5 years from first patient in

Secondary Outcomes (9)

• 2-year overall survival (OS) rate

  7.5 years from first patient in

• Other pathological response

  7.5 years from first patient in

• Probability of being event-free at 2 years

  7.5 years from first patient in

• Surgery rate

  7.5 years from first patient in

• Breast conservation rate

  7.5 years from first patient in

Other Outcomes (3)

• Exploratory endpoints: the impact of olaparib alone or olaparib in combination with durvalumab on ovarian function (in patients ≤ 50 years)

  7.5 years from first patient in

• Exploratory endpoints: Translational research

  7.5 years from first patient in

• Exploratory endpoints: To assess the evolution of the other scales HRQoL in both arms

  7.5 years from first patient in

Study Arms (2)

Olaparib

EXPERIMENTAL

Olaparib treatment for a total of 16 weeks

Drug: olaparib

Olaparib and durvalumab

EXPERIMENTAL

Olaparib and durvalumab treatment for a total of 16 weeks

Drug: olaparib; Drug: Durvalumab

Interventions

olaparib DRUG

olaparib 300 mg per os BID

Olaparib; Olaparib and durvalumab

Durvalumab DRUG

durvalumab 1500 mg IV Q4 weeks

Olaparib and durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Age ≥18 years
• Women and men can be included
• ECOG performance status (PS) 0-1

You may not qualify if:

• 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
• 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
• 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:

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• AstraZeneca: collaborator

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

olaparib; durvalumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Etienne Brain

  Institut Curie Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Eligible patients after central screening are randomized to olaparib vs olaparib and durvalumab

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: January 26, 2022
• Study Start: February 1, 2024
• Primary Completion (Estimated): September 6, 2028
• Study Completion (Estimated): July 18, 2030
• Last Updated: February 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share