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A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer (IMpassion132)

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ClinicalTrials.gov Identifier: NCT03371017
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE November 21, 2017
First Posted Date  ICMJE December 13, 2017
Last Update Posted Date March 13, 2019
Actual Study Start Date  ICMJE January 11, 2018
Estimated Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
Overall survival (OS) [ Time Frame: Randomization: 30 months post FPI ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03371017 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
  • Proportion of patients alive 12 months [ Time Frame: Randomization; 12 months post randomization ]
  • Proportion of patients alive 18 months [ Time Frame: Randomization; 18 months post randomization ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Neoplasms
Intervention  ICMJE
  • Drug: Atezolizumab

    Atezolizumab will be administered, 1200 mg by IV infusion with :

    gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

  • Drug: Placebo

    Placebo will be administered, 1200 mg by IV infusion with :

    gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

  • Drug: Gemcitabine
    Gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle
  • Drug: Capecitabine
    Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle
  • Drug: Carboplatin
    Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle
Study Arms
  • Experimental: Atezolizumab
    Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
    Interventions:
    • Drug: Atezolizumab
    • Drug: Gemcitabine
    • Drug: Capecitabine
    • Drug: Carboplatin
  • Placebo Comparator: Placebo
    Participants will receive Placebo on day 1 of each 3-week treatment cycle
    Interventions:
    • Drug: Placebo
    • Drug: Gemcitabine
    • Drug: Capecitabine
    • Drug: Carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 7, 2017)
350
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date January 31, 2021
Estimated Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Reference Study ID Number: MO39193 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE Algeria,   Bosnia and Herzegovina,   Brazil,   Cuba,   Finland,   France,   Germany,   Hungary,   Italy,   Kazakhstan,   Korea, Republic of,   Mexico,   Montenegro,   Morocco,   Panama,   Russian Federation,   Serbia,   Singapore,   South Africa,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03371017
Other Study ID Numbers  ICMJE MO39193
2016-005119-42 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP