E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Triple-Negative Breast Cancer (TNBC) |
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E.1.1.1 | Medical condition in easily understood language |
TNBC refers to a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PgR) or HER2/neu |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10075566 |
E.1.2 | Term | Triple negative breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the efficacy of atezolizumab plus chemotherapy compared to placebo plus chemotherapy based on overall survival |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of atezolizumab plus chemotherapy compared to placebo plus chemotherapy based on survival rate, progression free survival, objective response rate, duration of objective response, clinical benefit rate • To evaluate patient-reported outcomes (PROs) of global health status (GHS)/health-related quality of life (HRQoL) associated with atezolizumab plus chemotherapy compared with chemotherapy alone, as measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) • To evaluate the safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy • To characterize the pharmacokinetics (PK) of atezolizumab when administered with carboplatin/gemcitabine or with capecitabine in patients with breast cancer • To evaluate the immunogenicity of atezolizumab • To assess the efficacy and safety of atezolizumab plus chemotherapy according to programmed death−ligand 1 (PD-L1) status |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female >= 18 years of age - Histologically confirmed TNBC that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic - Documented disease progression occurring within 12 months (<12 months) from the last treatment with curative intent - Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence - Measurable or non-measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Availability of a representative formalin-fixed paraffin-embedded (FFPE) tumour block (preferred) or at least 25 unstained slides with an associated pathology report, if available - Eastern Cooperative Oncology Group performance status 0-1 - Life expectancy >= 12 weeks - Adequate haematologic and end-organ function, Negative human immunodeficiency virus (HIV) test at screening - Negative hepatitis B surface antigen (HBsAg) test at screening - Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening - Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening - The HCV RNA test will be performed only for patients who have a positive HCV antibody test - Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of <=1% per year during the treatment period and for at least 5 months after the last dose of study treatment - Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm, with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of carboplatin/gemcitabine to avoid exposing the embryo. |
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E.4 | Principal exclusion criteria |
- 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 randomisation - Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases - Symptomatic or rapid visceral progression - No prior treatment with an anthracycline and taxane - History of leptomeningeal disease - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures - Uncontrolled tumour-related pain - Uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy - Malignancies other than TNBC within 5 years prior to randomisation, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate 90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localised prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer) - Significant cardiovascular disease - Presence of an abnormal ECG that is clinically significant in the investigator’s opinion - Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia - Current treatment with anti-viral therapy for HBV - Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis - Treatment with investigational therapy within 28 days prior to randomisation - Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of study treatment |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. 12-month survival rate 2. 18-month survival rate 3. Progression-free survival 4. Objective response rate 5. Duration of objective response 6. Clinical benefit rate 7. Time to deterioration (TTD) of GHS/HRQoL 8. Incidence, nature and severity of adverse events (AEs), with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0) 9. Change from baseline in targeted vital signs and physical findings 10. Change from baseline in targeted clinical laboratory test results 11. Maximum and minimum observed serum concentration (Cmax and Cmin) of atezolizumab 12. Incidence of anti-drug antibodies (ADAs) during the study relative to the prevalence of ADAs at baseline. 13. Relationship between PD-L1 protein expression by immunohistochemistry (Ventana® SP142 assay) in screening tumour tissue and clinical outcomes
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Month 12 2. Month 18 3-13. Up to 36 months
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity and biomarker objectives |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Algeria |
Bosnia and Herzegovina |
Brazil |
Cuba |
Egypt |
France |
Germany |
Hong Kong |
Hungary |
Italy |
Kazakhstan |
Korea, Republic of |
Mexico |
Morocco |
Panama |
Russian Federation |
Serbia |
Singapore |
South Africa |
Spain |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the last patient last visit (LPLV). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 36 |