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A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC) (IMpassion131)

This study is currently recruiting participants.
Verified December 2017 by Hoffmann-La Roche
Sponsor:
ClinicalTrials.gov Identifier:
NCT03125902
First Posted: April 24, 2017
Last Update Posted: December 6, 2017
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.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
This Phase 3, multicenter, randomized, double-blind, placebo controlled study is designed to evaluate the efficacy and safety of atezolizumab (MPDL3280A, an anti-programmed death-ligand 1 [PD-L1] antibody) administered in combination with paclitaxel compared with placebo in combination with paclitaxel in participants with previously untreated, inoperable locally advanced or metastatic, centrally confirmed TNBC. Participants will be randomized in a 2:1 ratio to receive atezolizumab or placebo plus paclitaxel until disease progression or unacceptable toxicity or end of study, whichever occurs first (maximum up to approximately 45 months).

Condition Intervention Phase
Triple-Negative Breast Cancer Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody Drug: Atezolizumab Placebo Drug: Paclitaxel Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:
The Sponsor and its agents; the study site personnel, including the investigator; and the participant will be blinded to treatment assignment.
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomised, Double-Blind, Placebo-Controlled Study of Atezolizumab (Anti-Pd-L1 Antibody) in Combination With Paclitaxel Compared With Placebo With Paclitaxel for Patients With Previously Untreated Inoperable Locally Advanced or Metastatic Triple Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: From Day 1 to disease progression (PD) or death from any cause, assessed up to end of study (up to approximately 45 months) ]
    PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (>/=) 20 percent (%) relative increase and >/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.


Secondary Outcome Measures:
  • Percentage of Participants Who are Alive Without Progression Event at Month 12 Assessed Using RECIST v1.1 [ Time Frame: From Day 1 to PD or death from any cause, assessed up to 12 months ]
    PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.

  • Overall Survival (OS) [ Time Frame: From Day 1 to death from any cause, assessed up to end of study (up to approximately 45 months) ]
    OS is defined as the time from randomization to death from any cause.

  • Percentage of Participants Who are Alive at 12 and 18 Months [ Time Frame: From Day 1 to death from any cause, assessed up to 12 and 18 months ]
  • Time to deterioration (TTD) in Global Health Status/ Health Related Quality of Life (HRQoL) [ Time Frame: From Day 1 to deterioration, assessed up to end of study (up to approximately 45 months) ]
    Deterioration in Global Health Status/HRQoL is defined as a decrease of at least 10 points on the Global Health Status /HRQoL scale (comprised of 2 items: 29 and 30) of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The 2 items use 7-point scale (1 = very poor to 7 = Excellent). Scores are averaged, transformed to 0-100 scale; where higher score=better level of functioning or greater degree of symptoms.

  • Percentage of Participants With Objective Response Assessed Using RECIST v1.1 [ Time Frame: From Day 1 to PD, assessed up to end of study (up to approximately 45 months) ]
    Objective response is defined as complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD.

  • Duration of Objective Response (DOR) Assessed Using RECIST v1.1 [ Time Frame: From objective response to PD, assessed up to end of study (up to approximately 45 months) ]
    DOR is defined as the time period from the date of initial CR or PR until the date of PD or death from any cause, whichever occurs first. CR is defined as the disappearance of all TLs and SA reduction to <10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.

  • Percentage of Participants With Clinical Benefit Assessed Using RECIST v1.1 [ Time Frame: From Day 1 to PD, assessed up to end of study (up to approximately 45 months) ]
    Clinical benefit is defined as the achievement of CR, PR, or stable disease according to RECIST v1.1 that lasts for at least 6 months. CR is defined as the disappearance of all TLs and SA reduction to <10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference smallest SD since treatment started.

  • Minimum Observed Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16, and at every 8 cycles thereafter until treatment discontinuation (TD), and at 90-150 days after TD (maximum up to 45 months) (1 Cycle = 28 days) ]
  • Maximum Observed Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Please refer to measure description for time frame ]
    Pre-dose (0 hours), 20-40 minutes (min) after atezolizumab infusion on Day 1 Cycle 1, Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, 16, and at every 8 cycles thereafter until TD, and at 90-150 days after TD (maximum up to 45 months) (atezolizumab infusion duration= 45-75 min) (1 Cycle = 28 days)

  • Minimum Observed Plasma Concentration (Cmin) of Paclitaxel [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycles 1 and 3 (1 Cycle = 28 days) ]
  • Maximum Observed Plasma Concentration (Cmax) of Paclitaxel [ Time Frame: Pre-dose (0 hours), 5-10 min before and after paclitaxel infusion, 60 min after paclitaxel infusion on Day 1 of Cycles 1 and 3 (paclitaxel infusion duration= 60 min) (1 Cycle = 28 days) ]
  • Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: From Day 1 to 90 days after last dose of study drug, assessed up to end of study (up to approximately 45 months) ]
  • Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16, and at every 8 cycles thereafter until TD, at TD, and at 90-150 days after TD (maximum up to 45 months) (1 Cycle = 28 days) ]
  • Change From Baseline in PD-L1 Expression by Immunohistochemistry at Approximately 45 Months [ Time Frame: From Day 1 up to end of study (up to approximately 45 months) ]

Estimated Enrollment: 540
Actual Study Start Date: August 25, 2017
Estimated Study Completion Date: June 30, 2021
Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atezolizumab and Paclitaxel
Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.
Other Name: MPDL3280A, TECENTRIQ
Drug: Paclitaxel
Paclitaxel will be administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.
Placebo Comparator: Placebo and Paclitaxel
Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.
Drug: Atezolizumab Placebo
Placebo matching to atezolizumab will be administered via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.
Drug: Paclitaxel
Paclitaxel will be administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with locally advanced or metastatic, histologically documented TNBC (absence of human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER], and progesterone receptor [PR] expression), not amenable to surgical therapy
  • Participants eligible for taxane monotherapy
  • No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for inoperable locally advanced or metastatic TNBC
  • Availability of formalin-fixed paraffin-embedded (FFPE) tumor block (preferred) or at least 25 unstained slides, collected ≤3 months prior to randomization, with an associated pathology report
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Life expectancy at least 12 weeks
  • Measurable disease, as defined by RECIST v1.1
  • Adequate hematologic and end-organ function
  • Women of child bearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug
  • For men and women of child bearing potential: agreement to remain abstinent or use protocol defined contraceptive measures during the treatment period and for at least 5 months after the last dose of atezolizumab/placebo, or for at least 6 months after the last dose of paclitaxel

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 at least 2 weeks prior to randomization
  • Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
  • Leptomeningeal disease
  • Uncontrolled pleural effusion, pericardial effusion, or ascites
  • Uncontrolled tumor-related pain, or uncontrolled hypercalcemia or clinically significant (symptomatic) hypercalcemia
  • Malignancies other than TNBC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)
  • Pregnant or breast-feeding women, or intending to become pregnant during the study
  • Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease, cardiovascular disease, and presence of an abnormal electrocardiogram (ECG)
  • Serious infection requiring antibiotics within 2 weeks prior to randomization, including but not limited to infections requiring hospitalization or IV antibiotics, such as bacteremia, or severe pneumonia
  • Major surgical procedure within 4 weeks prior to randomization or anticipation of the need for a major surgical procedure during the study other than for diagnosis
  • Treatment with investigational therapy within 30 days prior to initiation of study treatment
  • History of hypersensitivity reactions to study drug or any component of the study drug formulation
  Contacts and Locations
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): NCT03125902


Contacts
Contact: Reference Study ID Number: MO39196 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 159 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Additional Information:
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03125902     History of Changes
Other Study ID Numbers: MO39196
2016-004024-29 ( EudraCT Number )
First Submitted: April 20, 2017
First Posted: April 24, 2017
Last Update Posted: December 6, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Atezolizumab
Albumin-Bound Paclitaxel
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs