Clinical Trials /

A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer

NCT03371017

Description:

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: MO39193
  • SECONDARY ID: 2016-005119-42
  • NCT ID: NCT03371017

Conditions

  • Triple Negative Breast Neoplasms

Interventions

DrugSynonymsArms
AtezolizumabAtezolizumab
PlaceboPlacebo
GemcitabineAtezolizumab
CapecitabineAtezolizumab
CarboplatinAtezolizumab

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
AtezolizumabExperimentalParticipants will receive Atezolizumab on day 1 of each 3-week treatment cycle
  • Atezolizumab
  • Gemcitabine
  • Capecitabine
  • Carboplatin
PlaceboPlacebo ComparatorParticipants will receive Placebo on day 1 of each 3-week treatment cycle
  • Placebo
  • Gemcitabine
  • Capecitabine
  • Carboplatin

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

          -  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 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 ---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

          -  The HBV DNA test will be performed only for patients who have a positive HBcAb test

          -  Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
             test followed by a negative HCV RNA test at screening.

          -  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

        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

          -  Presence of an abnormal ECG

          -  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

        Exclusion Criteria Related to Atezolizumab:

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanised antibodies or fusion proteins

          -  Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
             ovary cells or to any component of the atezolizumab formulation

          -  History of autoimmune disease

          -  Prior allogeneic stem cell or solid organ transplantation

          -  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
             computerised tomography (CT) scan History of radiation pneumonitis in the radiation
             field (fibrosis) is permitted.

          -  Active tuberculosis

          -  Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or
             anticipation that a live, attenuated vaccine will be required during
             atezolizumab/placebo treatment or within 5 months after the last dose of
             atezolizumab/placebo

          -  Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or
             pathway targeting agents

          -  Treatment with systemic immunostimulatory agents (including but not limited to
             interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug
             (whichever is longer) prior to randomisation

          -  Treatment with systemic corticosteroids or other systemic immunosuppressive
             medications within 2 weeks prior to randomisation, or anticipated requirement for
             systemic immunosuppressive medications during the trial

        Exclusion Criteria Related to Capecitabine:

          -  Inability to swallow pills

          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function,
             resection of the stomach or small bowel, or ulcerative colitis

          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and
             unexpected reactions to fluoropyrimidine therapy in patients selected to receive
             capecitabine

        Exclusion Criteria Related to Carboplatin/Gemcitabine:

        -Hypersensitivity to platinum containing compounds or any component of carboplatin or
        gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Randomization: 30 months post FPI
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Proportion of patients alive 12 months
Time Frame:Randomization; 12 months post randomization
Safety Issue:
Description:
Measure:Proportion of patients alive 18 months
Time Frame:Randomization; 18 months post randomization
Safety Issue:
Description:
Measure:Progression-free survival (PFS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Time Frame:Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 36 months)
Safety Issue:
Description:
Measure:Objective response rate (ORR), defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1
Time Frame:Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until PD, withdrawal of consent, death, or study termination (approximately 36 months)
Safety Issue:
Description:
Measure:Duration of objective response (DoR) as determined by the investigator according to RECIST 1.1
Time Frame:Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 36 months)
Safety Issue:
Description:
Measure:Clinical benefit rate (CBR), defined as the proportion of patients with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1
Time Frame:8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 36 months)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

December 22, 2017