Study comparing Atezolizumab (anti-PD-L1 antibody) in combination with adjuvant anthracycline/taxane chemotherapy versus chemotherapy alone in patients with operable triple-negative breast cancer
Summary description of the study
The aim of this study is to compare the positive and negative effects of chemotherapy when administered with or without the new drug Atezolizumab. The goal is to find out whether the additional administration of Atezolizumab during chemotherapy better prevents the recurrence of triple-negative breast cancer. Triple-negative breast cancer means that the three most common types of receptors known to promote breast cancer growth - estrogen, progesterone, and the HER2/NEU gene, are not present in the cancer tumor. This is an open-label study. This means that the study doctor and study staff will know which treatment patients will receive. The study is divided into three phases: Pre-treatment phase (screening), treatment phase (approximately 53 weeks), and follow-up phase (approximately 60 months/5 years). Patients will be randomly assigned by a computer program to one of the following treatment groups: Atezolizumab + chemotherapy or chemotherapy alone. The odds are 1:1 of being assigned to either group. Chemotherapy will be administered intravenously (into the vein or via a central venous catheter). The chemotherapy drugs you receive are typically used to treat your type of breast cancer. Approximately 2300 adult patients will participate in this study at around 370 – 450 trial centers worldwide. In Switzerland, approximately 39 patients will participate at 3 trial centers. Participation in the study will last a maximum of 7 years.
(BASEC)
Intervention under investigation
This clinical study is conducted to determine whether the drug Atezolizumab is safe and useful in the adjuvant treatment (after surgery) in combination with chemotherapy consisting of Paclitaxel, dose-dense Doxorubicin or Epirubicin* (depending on the decision of the study doctor) and Cyclophosphamide (T-AC/EC), compared to chemotherapy alone in patients with triple-negative breast cancer (TNBC) stage II to III.
*Dose-dense chemotherapy increases the strength of the dosage of the treatment regimen by administering standard-dose chemotherapy at shorter intervals between treatment periods.
(BASEC)
Disease under investigation
Operable triple-negative breast cancer
(BASEC)
1. Male and female patients who are ≥ 18 years old at the time of signing the patient information and informed consent 2. ECOG performance status (Eastern Cooperative Oncology Group) 0 or 1 3. Operable, non-metastatic breast cancer stage II−III (BASEC)
Exclusion criteria
1. History of invasive breast cancer 2. For the currently diagnosed breast cancer: previous systemic treatment (e.g., neoadjuvant or adjuvant), particularly chemotherapy, anti-HER2 therapy (e.g., Trastuzumab, Trastuzumab-Emtansine, Pertuzumab, Lapatinib, Neratinib, or other tyrosine kinase inhibitors), hormone therapy, or cancer RT that is not planned in the context of the study 3. For women: pregnancy, breastfeeding, or the desire to become pregnant during the study (BASEC)
Trial sites
Aarau, Lausanne, Zurich
(BASEC)
Sponsor
not available
Contact
General Information
Hoffmann-La Roche
(ICTRP)
Scientific Information
Hoffmann-La Roche
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Bern
(BASEC)
Date of authorisation
16.04.2019
(BASEC)
ICTRP Trial ID
NCT03498716 (ICTRP)
Official title (approved by ethics committee)
not available
Academic title
A Phase III, Multicenter, Randomized, Open-Label Study Comparing Atezolizumab (Anti PD-L1 Antibody) in Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone in Patients With Operable Triple Negative Breast Cancer (ICTRP)
Public title
A Study Comparing Atezolizumab (Anti PD-L1 Antibody) In Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone In Patients With Operable Triple-Negative Breast Cancer (ICTRP)
Disease under investigation
Triple Negative Breast Cancer (ICTRP)
Intervention under investigation
Drug: Atezolizumab;Drug: Paclitaxel;Drug: Dose-dense Doxorubicin or dose-dense Epirubicin;Drug: Cyclophosphamide (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
Gender: All
Maximum age: N/A
Minimum age: 18 Years
Inclusion Criteria:
- Non-metastatic operable Stage II-III breast cancer
- Histologically documented TNBC (Triple Negative Breast Cancer)
- Confirmed tumor PD-L1 evaluation as documented through central testing of a
representative tumor tissue specimen
- Adequately excised: Patients must have undergone either breast-conserving surgery or
mastectomy/nipple- or skin-sparing mastectomy
- Adequate hematologic and end-organ function
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures and agreement to refrain from donating sperm.
- No more than 8 weeks (56 days) may elapse between definitive breast surgery and
randomization.
- Representative formalin-fixed, paraffin embedded (FFPE) tumor specimen from surgical
resection in paraffin blocks (preferred) or at least 25 unstained slides.
Exclusion Criteria
- Prior history of invasive breast cancer
- For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment
(e.g., neoadjuvant or adjuvant), including, but not limited to, chemotherapy,
anti-HER2 therapy.
- Previous therapy with anthracyclines or taxanes for any malignancy
- Cardiopulmonary dysfunction
- Prior malignancies within 5 years prior to randomization, with the exception of those
with a negligible risk of metastasis or death and treated with expected curative
outcome
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography (CT) scan
- Urinary outflow obstruction
- Active tuberculosis
- Major surgical procedure other than for diagnosis within 4 weeks prior to initiation
of study treatment or anticipation of need for a major surgical procedure during study
treatment or within 5 months following the last dose of Atezolizumab (for patients
randomized to Atezolizumab)
- Prior allogeneic stem cell or solid organ transplant
- Treatment with systemic immunosuppressive medications within 2 weeks prior to
initiation of study treatment or anticipation of need for systemic immunosuppressive
medication during the study
(ICTRP)
not available
Primary and secondary end points
Invasive Disease-Free Survival (iDFS) (ICTRP)
Overall Survival (OS);Disease-Free Survival (DFS);Recurrence-Free Interval (RFI);Distant RFI;Percentage of participants with adverse events;Serum concentration of Atezolizumab;Invasive Disease-Free Survival (iDFS) in PDL1- Selected Patients;Invasive Disease-Free Survival (iDFS) in Node- Positive Disease;Invasive Disease Free Survival (iDFS) including second primary non-breast invasive cancer;Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab;Mean changes from baseline in patient-reported function (role, physical);Mean changes from baseline in patient-reported health-related quality of life (HRQoL) (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
Breast International Group;Alliance Foundation Trials (AFT);Institut Jules Bordet/Clinical Trials Support Unit (IJB/CTSU);Frontier Science & Technology Research Foundation, Inc. (ICTRP)
Additional contacts
Clinical Trials, Hoffmann-La Roche (ICTRP)
Secondary trial IDs
AFT-27, ALEXANDRA, 2016-003695-47, BIG 16-05, WO39391 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT03498716 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available