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

NCT ID: NCT05498896

Last Updated: 2025-03-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-19
• Study Completion Date: 2026-01-30

Brief Summary

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.

Conditions

Triple Negative Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezolizumab + Chemotherapy

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)

Group Type: OTHER

Atezolizumab

Intervention Type: DRUG

IV infusion

Paclitaxel

Intervention Type: DRUG

IV infusion

Doxorubicin

Intervention Type: DRUG

IV infusion

Cyclophosphamide

Intervention Type: DRUG

IV infusion

Atezolizumab + Chemotherapy + Ipatasertib

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).

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

IV infusion

Ipatasertib

Intervention Type: DRUG

Oral

Paclitaxel

Intervention Type: DRUG

IV infusion

Doxorubicin

Intervention Type: DRUG

IV infusion

Cyclophosphamide

Intervention Type: DRUG

IV infusion

Interventions

Atezolizumab

IV infusion

Intervention Type: DRUG

Ipatasertib

Oral

Intervention Type: DRUG

Paclitaxel

IV infusion

Intervention Type: DRUG

Doxorubicin

IV infusion

Intervention Type: DRUG

Cyclophosphamide

IV infusion

Intervention Type: DRUG

Other Intervention Names

Tecentriq

Eligibility Criteria

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

19. Current treatment with anti-viral therapy for HBV

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

21. 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.

22. Significant cardiovascular disease

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

23. 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

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

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

26. 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

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

28. Pregnant or nursing women

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

30. Clinically significant abnormalities of glucose metabolism

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Westdeutsche Studiengruppe GmbH (WSG)

UNKNOWN

Sponsor Role: collaborator

MedSIR

OTHER

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Queen Mary University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Schmid

Role: STUDY_CHAIR

Queen Mary University of London

Locations

Barts Health NHS Trust

London, , United Kingdom

Countries

United Kingdom

References

P. Schmid, F.J. Salvador Bofill, B. Bermejo, et al. BARBICAN: A randomized, phase II study to determine the contribution of ipatasertib to neoadjuvant chemotherapy plus atezolizumab in women with triple-negative breast cancer. Annals of Oncology (2021) 32 (suppl_5): S407-S446. 10.1016/annonc/annonc687

Reference Type: RESULT

Other Identifiers

2018-000977-62

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

012418QM

Identifier Type: -

Identifier Source: org_study_id