Clinical Trials /

A Study of Atezolizumab in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Participants With Previously Untreated Metastatic Triple-Negative Breast Cancer (IMpassion130)

NCT02425891

Description:

This multicenter, randomized, double-blind study will evaluate the efficacy, safety, and pharmacokinetics of atezolizumab (MPDL3280A) administered with nab-paclitaxel compared with placebo in combination with nab-paclitaxel in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic breast cancer (mBC). The safety of single-agent nab-paclitaxel has been determined in previous studies of participants with mBC and the safety data to date suggest that atezolizumab can be safely combined with standard chemotherapy agents.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Participants With Previously Untreated Metastatic Triple-Negative Breast Cancer (IMpassion130)
  • Official Title: A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Patients With Previously Untreated Metastatic Triple-Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: WO29522
  • SECONDARY ID: 2014-005490-37
  • NCT ID: NCT02425891

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibodyTecentriq, MPDL3280AAtezolizumab Plus Nab-Paclitaxel
Nab-PaclitaxelAbraxane®Atezolizumab Plus Nab-Paclitaxel
PlaceboPlacebo Plus Nab-Paclitaxel

Purpose

This multicenter, randomized, double-blind study will evaluate the efficacy, safety, and pharmacokinetics of atezolizumab (MPDL3280A) administered with nab-paclitaxel compared with placebo in combination with nab-paclitaxel in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic breast cancer (mBC). The safety of single-agent nab-paclitaxel has been determined in previous studies of participants with mBC and the safety data to date suggest that atezolizumab can be safely combined with standard chemotherapy agents.

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab Plus Nab-PaclitaxelExperimentalParticipants assigned to atezolizumab plus nab-paclitaxel will receive both agents until loss of clinical benefit, unacceptable toxicity, symptomatic deterioration attributed to disease progression, or death.
  • Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
  • Nab-Paclitaxel
Placebo Plus Nab-PaclitaxelPlacebo ComparatorParticipants assigned to placebo plus nab-paclitaxel will receive both agents until loss of clinical benefit, unacceptable toxicity, symptomatic deterioration attributed to disease progression, or death.
  • Nab-Paclitaxel
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Metastatic or locally advanced, histologically documented TNBC characterized by
             absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and
             progesterone receptor (PR) expression

          -  No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or
             metastatic TNBC

          -  Eligible for taxane monotherapy (i.e., absence of rapid clinical progression,
             life-threatening visceral metastases, or the need for rapid symptom and/or disease
             control)

          -  A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks,
             or at least 20 unstained slides with an associated pathology report documenting ER,
             PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at
             baseline, and not fewer than 12 unstained slides will be eligible upon discussion with
             Medical Monitor

          -  Eastern Cooperative Oncology Group performance status of 0 or 1

          -  Measurable disease as defined by RECIST v1.1

          -  Adequate hematologic and end-organ function

        Exclusion Criteria:

          -  Known central nervous system (CNS) disease, except for treated asymptomatic CNS
             metastases

          -  Leptomeningeal disease

          -  Pregnancy or lactation

          -  History of autoimmune disease

          -  Prior allogeneic stem cell or solid organ transplantation

          -  Positive test for human immunodeficiency virus

          -  Active hepatitis B or hepatitis C

          -  Receipt of a live, attenuated vaccine within 4 weeks prior to randomization, during
             treatment, or within 5 months following the last dose of atezolizumab/placebo
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) in all Randomized Participants
Time Frame:Baseline up to 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 in all Randomized Participants
Time Frame:Baseline up to 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first)
Safety Issue:
Description:
Measure:Percentage of Participants With an Objective Response of CR or PR According to RECIST v1.1 in Participants with Detectable PD-L1
Time Frame:Baseline up to 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first)
Safety Issue:
Description:
Measure:Duration of Response (DOR) According to RECIST v1.1 in all Randomized Participants
Time Frame:Baseline up to 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first)
Safety Issue:
Description:
Measure:DOR Acccording to RECIST v1.1 in Participants with Detectable PD-L1
Time Frame:Baseline up to 53 months (assessed at Screening, every 8 weeks for the first 12 months, thereafter every 12 weeks until disease progression or death, whichever occurs first)
Safety Issue:
Description:
Measure:Time to Deterioration (TTD) in Global Health Status/Health Related Quality of Life According to European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) v3.0 in all Randomized Participants
Time Frame:Baseline up to 53 months (assessed at Day 1 of each cycle up to treatment discontinuation [approximately 53 months], every 28 days after treatment discontinuation for 1 year [overall approximately 53 months]) (cycle = 28 days)
Safety Issue:
Description:
Measure:TTD in Global Health Status/Health Related Quality of Life According to EORTC QLQ-C30 v3.0 in Participants with Detectable PD-L1
Time Frame:Baseline up to 53 months (assessed at Day 1 of each cycle up to treatment discontinuation [approximately 53 months], every 28 days after treatment discontinuation for 1 year [overall approximately 53 months]) (cycle = 28 days)
Safety Issue:
Description:
Measure:Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs)
Time Frame:Baseline up to 53 months
Safety Issue:
Description:
Measure:Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
Time Frame:Baseline up to 53 months (assessed at pre-dose [Hour 0] on Day 1 of Cycles 1, 2, 3, 4, 8, 16, and every 8 cycles thereafter up to treatment discontinuation [approximately 53 months], 120 days after last dose [approximately 53 months]) (Cycle = 28 days)
Safety Issue:
Description:
Measure:Maximum Serum Concentration (Cmax) for Atezolizumab
Time Frame:Pre-dose (Hour 0) on Cycle 1 Day 1 up to 53 months (detailed timeframe is provided in outcome description section)
Safety Issue:
Description:Pre-dose (Hour 0), 30 minutes after end of atezolizumab infusion (infusion duration = 60 minutes) on Cycle 1 Day 1; pre-dose (Hour 0) on Day 1 of Cycles 2, 3, 4, 8, 16, and every 8 cycles thereafter up to treatment discontinuation (approximately 53 months), 120 days after last dose (approximately 53 months) (Cycle = 28 days)
Measure:Minimum Serum Concentration (Cmin) for Atezolizumab
Time Frame:Pre-dose (Hour 0) on Cycle 1 Day 1 up to 53 months (detailed timeframe is provided in outcome description section)
Safety Issue:
Description:Pre-dose (Hour 0), 30 minutes after end of atezolizumab infusion (infusion duration = 60 minutes) on Cycle 1 Day 1; pre-dose (Hour 0) on Day 1 of Cycles 2, 3, 4, 8, 16, and every 8 cycles thereafter up to treatment discontinuation (approximately 53 months), 120 days after last dose (approximately 53 months) (Cycle = 28 days)
Measure:Plasma Concentrations of Total Paclitaxel
Time Frame:Pre-dose (Hour 0) on Cycle 1 Day 1, pre-dose (Hour 0), 5-10 minutes before end of nab-paclitaxel infusion, 1 hour after end of nab-paclitaxel infusion (infusion duration = 30 minutes) on Cycle 3 Day 1 (Cycle = 28 days)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

January 8, 2018