Triple Negative Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tecentriq
Product Name: Tecentriq
Product Code: Atezolizumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN:
Sponsors
Queen Mary University of London
Eligibility
Sex/Gender
All
Inclusion 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 defined as: •ER negative with =65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: 1.Evidence of metastatic breast cancer. 2.Received any systemic therapy or radiotherapy for current breast cancer disease before study entry 3.Prior exposure to any CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-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; minor surgeries including insertion of an indwelling catheter, core needle biopsy, or sentinel lymph node biopsy is allowed. 8.Known intolerance to any of the study drugs 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 organizing pneumonia 13.History of HIV infection 14.Known active hepatitis infection or hepatitis C. 15.Active tuberculosis 16.Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia 17.Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics are eligible for the study. 18.Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab 19.Current treatment with anti-viral therapy for HBV 20.Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) 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 except in cases outlined below: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. Patients on stable low dose of corticosteroids for at least two weeks before randomisation are allowed. 22.Significant cardiovascular disease. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Clinical: To compare the pathologic complete response (pCR) rates of NACT plus atezolizumab with NACT plus atezolizumab plus Ipatasertib in patients with or without PIK3CA/AKT1/PTEN genetic alterations. Biological: To determine whether adding the AKT-inhibitor ipatasertib to atezolizumab and chemotherapy increases the probability of an immune response over adding atezolizumab to chemotherapy in all treated patients ; Secondary Objective: -Determine the response rates of the breast tumour and axillary nodes based on physical examination and imaging tests after treatment in both arms. -Assess clinical response rate after taxanes plus atezolizumab in both groups -To assess the effect of adding ipatasertib to atezolizumab on additional immune mediated biomarkers. -Determine the effect of ipatasertib on IEFS, DEFS and OS -Evaluate PROs of health-related quality of life (HRQoL) associated with the addition of ipatasertib, as measured by the EORTC QLQ-C30 -Assess the safety of each treatment arm. ; Primary end point(s): Clinical: • pCR is defined as no microscopic evidence of residual invasive tumour in all resected specimens of the breast and axilla (ypT0/is ypN0) in all patients • pCR is defined as no microscopic evidence of residual invasive tumour in all resected specimens of the breast and axilla (ypT0/is ypN0) in patients with or without PIK3CA/AKT1/PTEN genetic alterations Biological: 2-fold increase in GzmB+ CD8+ T cell levels from baseline to the end of each treatment phase ;Timepoint(s) of evaluation of this end point: At the time of definitive surgery following completion of study treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary: • Objective response rate (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 • ORR • Status and changes of the biomarkers listed below in pre- and end-of treatment tumour and/or blood samples: immune phenotyping, CD8, PD-L1 & MHC-I, immune infiltrates (IFNg gene signature expression) • IEFS, defined as the time from randomisation to date of first treatment failure that is invasive loco-regional or distant recurrence or new invasive cancer or death from any cause. IEFS is further detailed according to the standardized STEEP system definition as one of the following [13]: o Distant recurrence: metastatic disease-breast cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer o Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause o Ipsilateral invasive breast tumour recurrence (IIBTR): invasive breast cancer involving the same breast parenchyma as the original primary o Regional invasive breast cancer recurrence: Invasive breast cancer in the axilla, regional lymph nodes, chest wall, and skin of the ipsilateral breast. o Contralateralinvasivebreastcancer o Secondprimarynon-breastinvasivecancer • DEFS, defined as the time from randomisation to the date of first distant recurrence or death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Distant recurrence is defined as metastatic disease-breast cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer. • OS, defined as time from randomisation to death of | — |
Countries
Spain, United Kingdom
Contacts
Public ContactClinical Trial Unit
MEDICA SCIENTIA INNOVATION RESEARCH
Outcome results
None listed