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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03371017
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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).

Condition or disease Intervention/treatment Phase
Triple Negative Breast Neoplasms Drug: Atezolizumab Drug: Placebo Drug: Gemcitabine Drug: Capecitabine Drug: Carboplatin Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 572 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 11, 2018
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : August 2, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Atezolizumab
Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
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: 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

Placebo Comparator: Placebo
Participants will receive Placebo on day 1 of 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




Primary Outcome Measures :
  1. Overall Survival (OS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [ Time Frame: Baseline to end of study (approximately 58 months) ]

    OS will be tested hierarchically in the following fixed order:

    • In the population with programmed deathligand 1 (PD-L1)-positive tumour status
    • In the modified intent-to-treat (mITT) population

  2. Overall Survival (OS) in Modified Intent-To-Treat (mITT) Popluation [ Time Frame: Baseline to end of study (approximately 58 months) ]

    OS will be tested hierarchically in the following fixed order:

    • In the population with programmed deathligand 1 (PD-L1)-positive tumour status
    • In the modified intent-to-treat (mITT) population


Secondary Outcome Measures :
  1. Proportion of Participants Alive 12 Months [ Time Frame: Randomization to 12 months post randomization ]
  2. Proportion of Participants Alive 18 Months [ Time Frame: Randomization to 18 months post randomization ]
  3. Progression-Free Survival (PFS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [ Time Frame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months) ]

    PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.

    PFS will be tested hierarchically in the following fixed order:

    • In the PD-L1-positive population
    • In the mITT population

  4. Progression-Free Survival (PFS) in mITT population [ Time Frame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months) ]

    PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.

    PFS will be tested hierarchically in the following fixed order:

    • In the PD-L1-positive population
    • In the mITT population

  5. Objective Response Rate (ORR) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [ Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months) ]

    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. ORR will be tested hierarchically in the following fixed order:

    • In the PD-L1-positive population
    • In the mITT population

  6. Objective Response Rate (ORR) in Modified Intent-To-Treat (mITT) Popluation [ Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months) ]

    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. ORR will be tested hierarchically in the following fixed order:

    • In the PD-L1-positive population
    • In the mITT population

  7. Duration of Objective Response (DoR) [ Time Frame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months) ]
    DoR as determined by the investigator according to RECIST 1.1.

  8. Clinical Benefit Rate (CBR) [ 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 58 months) ]
    CBR is defined as the proportion of participants with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1.

  9. Confirmed Objective Response Rate (C-ORR) [ Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months) ]
  10. Duration of Response for Confirmed Responders (C-DoR) [ Time Frame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months) ]
  11. Time to deterioration (TTD) of GHS/QoL [ Time Frame: Baseline to end of study (approximately 58 months) ]
    TTD of GHS/QoL, defined by a minimally important decrease of ≥10 points at two consecutive assessment time-points on the GHS/QoL scale (Items 29, 30) of the EORTC QLQ-C30.

  12. Percentage of Participants With Adverse Events [ Time Frame: Baseline to end of study (approximately 58 months) ]
  13. Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days) ]
  14. Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days) ]
  15. Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Baseline to end of study (approximately 58 months) ]
  16. Relationship Between PD-L1 Protein Expression in Screening Tumour Tissue and Clinical Outcomes [ Time Frame: Baseline to end of study (approximately 58 months) ]
  17. Overall Survival (OS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [ Time Frame: Baseline to end of study (approximately 58 months) ]

    OS will be tested hierarchically in the following fixed order:

    • In the population with programmed deathligand 1 (PD-L1)-positive tumour status
    • In the modified intent-to-treat (mITT) population

  18. Overall Survival (OS) in mITT China Popluation [ Time Frame: Baseline to end of study (approximately 58 months) ]

    OS will be tested hierarchically in the following fixed order:

    • In the population with programmed deathligand 1 (PD-L1)-positive tumour status
    • In the modified intent-to-treat (mITT) population

  19. Proportion of Participants Alive 12 Months in China Population [ Time Frame: Randomization to 12 months post randomization ]
  20. Proportion of Participants Alive 18 Months in China Population [ Time Frame: Randomization to 18 months post randomization ]
  21. Progression Free Survival (PFS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [ Time Frame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months) ]

    PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.

    PFS will be tested hierarchically in the following fixed order:

    • In the PD-L1-positive population
    • In the mITT population

  22. Progression Free Survival (PFS) in mITT China Population [ Time Frame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months) ]

    PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.

    PFS will be tested hierarchically in the following fixed order:

    • In the PD-L1-positive population
    • In the mITT population

  23. Objective Response Rate (ORR) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status [ Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months) ]

    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. ORR will be tested hierarchically in the following fixed order:

    • In the PD-L1-positive population
    • In the mITT population

  24. ORR in Modified Intent-To-Treat (mITT) China Popluation [ Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months) ]

    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. ORR will be tested hierarchically in the following fixed order:

    • In the PD-L1-positive population
    • In the mITT population

  25. Duration of Objective Response (DoR) in China Population [ Time Frame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months) ]
    DoR as determined by the investigator according to RECIST 1.1.

  26. Clinical Benefit Rate (CBR) in China Population [ 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 58 months) ]
    CBR is defined as the proportion of participants with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1.

  27. Confirmed Objective Response Rate (C-ORR) in China Population [ Time Frame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months) ]
  28. Duration of Response for Confirmed Responders (C-DoR) in China Population [ Time Frame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months) ]
  29. Time to deterioration (TTD) of GHS/QoL in China Population [ Time Frame: Baseline to end of study (approximately 58 months) ]
    TTD of GHS/QoL, defined by a minimally important decrease of ≥10 points at two consecutive assessment time-points on the GHS/QoL scale (Items 29, 30) of the EORTC QLQ-C30.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, collected within 3 months prior to randomisation, with an associated pathology report, if available. If a tumour sample taken within 3 months before randomisation is not available and a tumour biopsy is not clinically feasible, the primary surgical resection sample or the most recent FFPE tumour biopsy sample may be used. Of these additional options, the most recent 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
  • 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 negative HBsAg and 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 atezolizumab or 6 months after the last dose of capecitabine, whichever is later. In addition, women must refrain from donating eggs during the same time period.
  • Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm

Inclusion criteria for patients enrolled after the recruitment of all-comers is complete:

-PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 expression on tumour-infiltrating immune cells (IC) of 1% or greater.

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 atezolizumab, or within 6 months after the last dose of capecitabine, whichever is later.

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03371017


Contacts
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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

Locations
Show Show 141 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03371017    
Other Study ID Numbers: MO39193
2016-005119-42 ( EudraCT Number )
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Carboplatin
Capecitabine
Atezolizumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs