Clinical Trials /

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

NCT03125902

Description:

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 40 months). In addition, the Sponsor may decide to terminate the study at any time.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MO39196
  • SECONDARY ID: 2016-004024-29
  • NCT ID: NCT03125902

Conditions

  • Triple-Negative Breast Cancer

Interventions

DrugSynonymsArms
Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibodyMPDL3280A, TECENTRIQAtezolizumab and Paclitaxel
Atezolizumab PlaceboPlacebo and Paclitaxel
PaclitaxelAtezolizumab and Paclitaxel

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).

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab and PaclitaxelExperimentalParticipants 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.
  • Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
  • Paclitaxel
Placebo and PaclitaxelPlacebo ComparatorParticipants 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.
  • Atezolizumab Placebo
  • Paclitaxel

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description: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

Measure: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
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:From Day 1 to death from any cause, assessed up to end of study (up to approximately 45 months)
Safety Issue:
Description:OS is defined as the time from randomization to death from any cause.
Measure: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
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:
Measure:Maximum Observed Serum Concentration (Cmax) of Atezolizumab
Time Frame:Please refer to measure description for time frame
Safety Issue:
Description: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)
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

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

Last Updated

June 12, 2017