Clinical Trials/NCT03371017

NCT03371017

Completed

Phase 3

A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicentre Study Of The Efficacy And Safety Of Atezolizumab Plus Chemotherapy For Patients With Early Relapsing Recurrent (Inoperable Locally Advanced Or Metastatic) Triple-Negative Breast Cancer

Hoffmann-La Roche124 sites in 18 countries595 target enrollmentJanuary 11, 2018

ConditionsTriple Negative Breast Neoplasms

InterventionsAtezolizumab Gemcitabine Capecitabine Carboplatin Placebo

Overview

Phase: Phase 3
Intervention: Atezolizumab
Conditions: Triple Negative Breast Neoplasms
Sponsor: Hoffmann-La Roche
Enrollment: 595
Locations: 124
Primary Endpoint: Overall Survival (OS) in PD-L1-positive Population
Status: Completed
Last Updated: 5 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study will evaluate the efficacy and safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy in patients with inoperable recurrent triple-negative breast cancer (TNBC).

Registry

clinicaltrials.gov

Start Date

January 11, 2018

End Date

October 23, 2024

Last Updated

5 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed triple negative breast cancer (TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
•Documented disease progression occurring within 12 months from the last treatment with curative intent
•Prior treatment (of early breast cancer) with an anthracycline and taxane
•Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permitted
•Measurable or non-measurable disease, as defined by RECIST 1.1
•Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block (preferred) or at least 17 unstained slides obtained from relapsed metastatic or locally advanced diseases may be submitted, if clinically feasible, with an associated pathology report, if available. If a fresh tumour sample is not clinically feasible, either the diagnosis sample, the primary surgical resection sample, or the most recent FFPE tumour biopsy sample should be used.
•Eastern Cooperative Oncology Group performance status 0-1
•Life expectancy ≥ 12 weeks
•Adequate haematologic and end-organ function
•Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening

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 (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed)
•Uncontrolled tumour-related pain
•Uncontrolled or symptomatic hypercalcemia
•Malignancies other than TNBC within 5 years prior to randomisation)
•Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina

Arms & Interventions

Atezolizumab

Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle

Intervention: Atezolizumab

Atezolizumab

Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle

Intervention: Gemcitabine

Atezolizumab

Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle

Intervention: Capecitabine

Atezolizumab

Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle

Intervention: Carboplatin

Placebo

Participants will receive Placebo on day 1 of each 3-week treatment cycle

Intervention: Placebo

Placebo

Participants will receive Placebo on day 1 of each 3-week treatment cycle

Intervention: Gemcitabine

Placebo

Participants will receive Placebo on day 1 of each 3-week treatment cycle

Intervention: Capecitabine

Placebo

Participants will receive Placebo on day 1 of each 3-week treatment cycle

Intervention: Carboplatin

Outcomes

Primary Outcomes

Overall Survival (OS) in PD-L1-positive Population

Time Frame: Time from randomization to death (Up to 68 months)

OS was defined as time from randomization to death from any cause. Participants without a reported death event at the time of the analysis were censored on the date they were last known to be alive. If no post-baseline data were available, OS was censored at the date of randomization +1 day.

OS in Modified Intent-to-treat (mITT) Population

Time Frame: Time from randomization to death (Up to 68 months)

Secondary Outcomes

12-month Survival Rate in PD-L1-positive Population(12 months)
12-month Survival Rate in mITT Population(12 months)
18-month Survival Rate in PD-L1-positive Population(18 months)
18-month Survival Rate in mITT Population(18 months)
Progression-free Survival (PFS) in PD-L1-positive Population(Time from randomization to the first occurrence of PD or death (Up to 68 months))
PFS in mITT Population(Time from randomization to the first occurrence of PD or death (Up to 68 months))
Objective Response Rate (ORR) in Response-evaluable Population, Subset of PD-L1-positive Population(Baseline up to end of study (Up to 68 months))
ORR in Response-evaluable Population, Subset of mITT Population(Baseline up to end of study (Up to 68 months))
Duration of Objective Response (DoR) in DoR-evaluable Population Subset of PD-L1-positive Population(Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months))
DoR in DoR-evaluable Population Subset of mITT Population(Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months))
Clinical Benefit Rate (CBR) in Response-evaluable Population Subset of PD-L1-positive Population(Up to 68 months)
CBR in Response-evaluable Population Subset of mITT Population(Up to 68 months)
Confirmed Objective Response Rate (C-ORR) in Response-evaluable Population Subset of PD-L1-positive Population(Up to 68 months)
C-ORR in Response-evaluable Population Subset of mITT Population(Up to 68 months)
DoR for Confirmed Responders (C-DoR) in C-DoR-evaluable Population Subset of PD-L1-positive Population(Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months))
C-DoR in C-DoR-evaluable Population Subset of mITT Population(Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months))
Time to Confirmed Deterioration (TTD) in Global Health Status/Quality of Life (GHS/QoL) According to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) in PD-L1-positive Population(Up to 68 months)
TTD in GHS/QoL According to EORTC QLQ-C30 in mITT Population(Up to 68 months)
Number of Participants With Adverse Events (AEs)(From treatment initiation up to 90 days after last dose (up to 71 months))
Serum Concentration of Atezolizumab(Pre-dose on Day 1 of Cycles 1, 2, 3 and 4; Post-dose on Day 1 of Cycles 1 and 3 and Treatment Discontinuation Visit (up to 69 months) (1 Cycle= 3 weeks))
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Cycles 1 to 4 and Treatment Discontinuation visit (up to 69 months))
Number of Participants With PD-L1 Protein Expression in Screening Tumour Tissue and Post-baseline Assessment(Baseline up to 68 months)