Investigate the Contribution of Ipatasertib to Neoadjuvant Chemotherapy Plus Atezolizumab in TNBC (BARBICAN)

Queen Mary University of London

Status and phase: Active, not recruiting; Phase 2

Conditions: Triple Negative Breast Cancer

Treatments: Drug: Doxorubicin; Drug: Ipatasertib; Drug: Cyclophosphamide; Drug: Atezolizumab; Drug: Paclitaxel

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05498896

012418QM

2018-000977-62 (EudraCT Number)

Details and patient eligibility

About

International, randomised, open label, neo-adjuvant phase II trial in women with newly diagnosed, non-metastatic, high-risk (node positive and/or tumour size ≥ 2cm), triple negative breast cancer. The study aims to evaluate the effects of adding ipatasertib to chemotherapy and atezolizumab in patients with and without PI3CA/AKT1/PTEN genetic alterations.

Enrollment: 146 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Willing and able to provide written informed consent prior to study entry
2. Female ≥ 18 years of age
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
4. Histologically confirmed TNBC
5. Node-positive (cT1-4 cN1-2 M0) and/or tumour size ≥2 cm (cT2-T4 cN0-2 M0) with no prior treatment
6. Adequate haematologic and end-organ function .
7. Patients of childbearing potential are eligible provided they have a negative serum or urine pregnancy test. Patients must agree to use adequate contraception
8. Ability to comply with the protocol
9. Representative formalin-fixed paraffin embedded breast tumour samples with an associated pathology report, determined to be available and sufficient for central testing OR tumour accessible for biopsy

Exclusion criteria

1. Evidence of metastatic breast cancer.

2. Any systemic therapy (e.g. chemotherapy, targeted therapy, immune-therapy) or radiotherapy for current breast cancer disease before study entry

3. Prior exposure to any CD137 agonists or immune checkpoint blockade therapies, including antiCTLA-4, anti-PD-1 or anti-PD-L1 antibody

4. Concurrent bilateral invasive breast cancer

5. Inflammatory breast cancer

6. Active malignancy (except for non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in-situ) within the past 36 months prior to study entry

7. Major surgery within the last 28 days or anticipation of the need for major surgery during study treatment

8. Known intolerance to any of the study drugs (ie, paclitaxel, doxorubicin, epirubicin, cyclophosphamide) or any of their excipients

9. Pre-existing peripheral neuropathy grade ≥ 2

10. History of autoimmune disease

11. History of Type I or Type II diabetes mellitus requiring insulin. Patients who are on a stable dose of oral diabetes medication ≥ 2 weeks prior to initiation of study treatment are eligible for enrolment

12. History of idiopathic pulmonary fibrosis or organising pneumonia

13. History of HIV infection

14. Known active hepatitis infection or hepatitis C.

15. Active tuberculosis

16. Current treatment with anti-viral therapy for HBV

17. Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment

18. Patients receiving concomitant immunosuppressive agents or chronic systemic corticosteroids (≥10 mg prednisolone or an equivalent dose of other anti-inflammatory corticosteroids) use for ≥28 days at the time of study entry.

19. Significant cardiovascular disease

20. Severe infection within 4 weeks prior to initiation of study treatment

21. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent

22. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol

23. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study entry

24. Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug

25. Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and peripheral neuropathy

26. Pregnant or nursing women

27. Inability to swallow medication or malabsorption condition that would alter the absorption of orally administered medications

28. Clinically significant abnormalities of glucose metabolism

29. History of or active inflammatory bowel disease or active bowel inflammation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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146 participants in 2 patient groups

Atezolizumab + Chemotherapy

Other group

Description:

Atezolizumab (1200mg IV Q3W x 1 cycle) followed by Paclitaxel (80 mg/m2 Q1W x 12) plus Atezolizumab 840 mg (Q2W x 6) followed by Doxorubicin (60 mg/m2) plus Cyclophosphamide (600 mg/m2 Q2W x 4) plus Atezolizumab (840 mg Q2W x 4)

Treatment:

Drug: Paclitaxel

Drug: Atezolizumab

Drug: Cyclophosphamide

Drug: Doxorubicin

Atezolizumab + Chemotherapy + Ipatasertib

Experimental group

Description:

Atezolizumab (1200 mg, Q3W x 1 cycle), plus Ipatasertib (400 mg OD, days 1-14) followed by Paclitaxel (80 mg/m2 Q1W x 12) plus Atezolizumab (840 mg Q2W x 6), plus Ipatasertib, (400 mg OD, days 1-21 Q4W) followed by Doxorubicin (60 mg/m2) plus Cyclophosphamide (600 mg/m2 Q2W x 4) plus Atezolizumab (840 mg Q2W x 4).

Treatment:

Drug: Paclitaxel

Drug: Atezolizumab

Drug: Cyclophosphamide

Drug: Ipatasertib

Drug: Doxorubicin