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

Sponsor

Queen Mary University of London (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05498896

Collaborator

Westdeutsche Studiengruppe GmbH (WSG) (Other), MedSIR (Other), Hoffmann-La Roche (Industry)

146

Enrollment

Location

Arms

85.4

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Cancer	Drug: Atezolizumab Drug: Ipatasertib Drug: Paclitaxel Drug: Doxorubicin Drug: Cyclophosphamide	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

146 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomised, Open-label Phase II Study to Determine the Contribution of Ipatasertib to Neoadjuvant Chemotherapy Plus Atezolizumab in Women With Triple-negative Breast Cancer

Actual Study Start Date :

Dec 19, 2018

Actual Primary Completion Date :

Jan 29, 2021

Anticipated Study Completion Date :

Jan 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Other: 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)	Drug: Atezolizumab IV infusion Other Names: Tecentriq Drug: Paclitaxel IV infusion Drug: Doxorubicin IV infusion Drug: Cyclophosphamide IV infusion
Experimental: 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).	Drug: Atezolizumab IV infusion Other Names: Tecentriq Drug: Ipatasertib Oral Drug: Paclitaxel IV infusion Drug: Doxorubicin IV infusion Drug: Cyclophosphamide IV infusion

Arm

Intervention/Treatment

Other: 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)

Drug: Atezolizumab

IV infusion

Other Names:

Tecentriq

Drug: Paclitaxel

IV infusion

Drug: Doxorubicin

IV infusion

Drug: Cyclophosphamide

IV infusion

Experimental: 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).

Drug: Atezolizumab

IV infusion

Other Names:

Tecentriq

Drug: Ipatasertib

Oral

Drug: Paclitaxel

IV infusion

Drug: Doxorubicin

IV infusion

Drug: Cyclophosphamide

IV infusion

Outcome Measures

Primary Outcome Measures

pCR [Time of definitive surgery (6 months after start of treatment)]
pCR defined as no microscopic evidence of residual invasive tumour

Secondary Outcome Measures

ORR [5 years]
ORR as assessed by RECIST 1.1 principles, defined as percentage of subjects with best overall response of complete response (CR) or partial response (PR) in the relevant analysis population.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Willing and able to provide written informed consent prior to study entry
Female ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
Histologically confirmed TNBC
Node-positive (cT1-4 cN1-2 M0) and/or tumour size ≥2 cm (cT2-T4 cN0-2 M0) with no prior treatment
Adequate haematologic and end-organ function .
Patients of childbearing potential are eligible provided they have a negative serum or urine pregnancy test. Patients must agree to use adequate contraception
Ability to comply with the protocol
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:

Evidence of metastatic breast cancer.
Any systemic therapy (e.g. chemotherapy, targeted therapy, immune-therapy) or radiotherapy for current breast cancer disease before study entry
Prior exposure to any CD137 agonists or immune checkpoint blockade therapies, including antiCTLA-4, anti-PD-1 or anti-PD-L1 antibody
Concurrent bilateral invasive breast cancer
Inflammatory breast cancer
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
Major surgery within the last 28 days or anticipation of the need for major surgery during study treatment
Known intolerance to any of the study drugs (ie, paclitaxel, doxorubicin, epirubicin, cyclophosphamide) or any of their excipients
Pre-existing peripheral neuropathy grade ≥ 2
History of autoimmune disease
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
History of idiopathic pulmonary fibrosis or organising pneumonia
History of HIV infection
Known active hepatitis infection or hepatitis C.
Active tuberculosis
Current treatment with anti-viral therapy for HBV
Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
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.
Significant cardiovascular disease
Severe infection within 4 weeks prior to initiation of study treatment
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
Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol
Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study entry
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
Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and peripheral neuropathy
Pregnant or nursing women
Inability to swallow medication or malabsorption condition that would alter the absorption of orally administered medications
Clinically significant abnormalities of glucose metabolism
History of or active inflammatory bowel disease or active bowel inflammation