Triple-negative breast cancer patients With matasteses MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tecentriq
Product Name: Atezolizumab
Product Code: MPDL3280A-RO5541267-F-03
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Oth
Sponsors
Oslo University Hospital (OUS)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Metastatic or incurable locally advanced, histologically documented TNBC 2. Adequate newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. No anti-tumor treatment is allowed between the time point for biopsy and study entry. If a patient has undergone chemotherapy in the metastatic setting, a new biopsy must be obtained after this therapy 3. Measurable disease according to iRECIST 4. Signed Informed Consent Form 5. Women or men aged = 18 years 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 7. A minimum of 12 months from (neo)adjuvant treatment with anthracyclines or cyclophosphamide until relapse of disease 8. A maximum of one previous line with chemotherapy in the metastatic setting 9. Female subject of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. 10. Female subjects of childbearing potential should agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Malignancies other than TNBC 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 2. Patients with known PD-L1 positive TNBC, and no previous chemotherapy in the metastatic setting, should be offered standard therapy with nab-paclitaxel/atezolizumab outside of the trial. Please see detailed considerations section 5.0 in the protocol. 3. Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization 4. Known CNS disease, except for asymptomatic CNS metastases, provided the criterias, section 5.0 in the protocol. 5. Uncontrolled pleural effusion, pericardial effusion, or ascites. Patients with indwelling catheters (e.g., PleurX®) are allowed 6. Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry. 7. Ionized calcium > 1.2 x UNL. The use of bisphosphonates is allowed 8. Pregnant or breastfeeding 9. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results 10.Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina. 11. Severe infection within 14 days prior to randomization, requiring hospitalization 12. Received oral or IV antibiotics within 1 week prior to Cycle 1, Day 1. Patients receiving routine antibiotic prophylaxis are eligible 13. Major surgical procedure within 14 days prior to randomization or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis. 14. A history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 15. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation 16. Known hypersensitivity to doxorubicin or cyclophosphamide or any of their excipients 17. A history of autoimmune disease that has required systemic treatment in the past 2 years. For further details/exceptions, see section 5.0 in the protocol 18. Undergone allogeneic stem cell or solid organ transplantation 19. A history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. 20. A positive test for HIV 21. Active hepatitis B or hepatitis C. 22. Active tuberculosis 23. Currently receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment 24. Received treatment with immune checkpoint modulators, including anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapeutic antibodies 25. Received treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization 26. Received treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: We expect to reach the data-driven time point for PFS-analysis (95% PFS events in all patients and in PD-L1 positive PP) 2.5-3 years after the study opens. lf this is not met within 18 months after inclusion of the last patient, the PFS analysis will beperformed at this time point.;Main Objective: - Assessment of toxicity of combined treatment with atezolizumab, pegylated liposomal doxorubicin and cyclophosphamide - Assessment of clinical response: Progression-free survival; descriptive comparison of the PFS rates in the total per protocol (PP) population, and the PD-L1+ PP population;Secondary Objective: Secondary objective: - Assessment of clinical response: Overall tumor response rate (ORR), duration of response (DR), durable tumor response rate (DRR; >6 months), overall survival (OS) - Assessment of changes in imminological milieu in tumor and peripheral blood - Assessment of PD-L1 expression - Assessment of patient reported outcomes, as measured by the Chalder Fatigue Questionnaire (FQ), an 11 point Numerical Rating Scale (NRS) for pain intensity and EORTC QLQ-C15-PAL Exploratory objectives: - Assessment of immunological response - ldentification of biomarkers for clinical response, toxicity and immune response - Characterization of tumor evolution induced by the study therapy concidering each study arm separately, and by comparing arm A to B - Characterization of changes in microbiota induced by the study therapy, considering each study arm separately, and by comparing arm A to arm B ;Primary end point(s): PFS, defined as the time from randomization to the time of disease (as assessed by irRECIST) or death from any cause during the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy outcome measures will beassessed in the ITT population and in the PD-L1-positive subpopulation as follows: - Overall survival (OS), defined as the time from the date of randomization to the date of death from any cause - Objective tumor response rate (ORR), defined as the proportion of patients with an objective tumor response (either partial response [PR] or complete response [CR] per investigator using irRECIST) - Durable response rate (DRR), defined as the proportion of patients with an objective tumor response lasting at least 6 months - Duration of objective response (DOR) among patients with an objective response - PFS in the PD-L1-negative subpopulation assessed by irRECIST - PFS, ORR, DRR and DOR assessed by RECIST v1.1 - lnvestigator-assessed PFS using irRECIST, with no censoring at missing scans - lnvestigator-assessed PFS using RECIST v1.1, with no censoring at missing scans Safety Outcome Measures - lncidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0 and AESls for atezolizumab. - Changes in vital signs, physical findings, and clinical laboratory results Exploratory Outcome Measures Assessment of immunological response: - ldentification of biomarkers for clinical response, toxicity and immune response - Characterization of tumor evolution and changes in immunological milieu induced by the combination therapy (atezolizumab+chemo), as compared to chemo only - Development in FQ score(11). The analyses will include time to deterioration (TTD) in the FQ score, defined bya minimally clinically important difference (MCID) of = 3 points. The maximum total FQ score is 33 points. For mean score, a separate analysis will beperfomed for subjects with a baseline FQ score = 21 points - Development in NRS pain intensity score for average pain the last 24 hours (corresponding to one item in BPI). The analyses will include TTD in the pain intensity score, defined by a minimally clinically | — |
Countries
Denmark, Norway
Contacts
Public ContactPrincipal Investigator
Oslo University Hospital
Outcome results
None listed