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) - Full Text View

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.

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


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Investigator Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer

Drug Information available for: Paclitaxel Atezolizumab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

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) ]
PFS According to RECIST v1.1 in Participants with Detectable Programmed Death-Ligand 1 (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) ]
Overall Survival (OS) in all Randomized Participants [ Time Frame: Baseline until death due to any cause (up to 53 months) ]
OS in Participants with Detectable PD-L1 [ Time Frame: Baseline until death due to any cause (up to 53 months) ]

Secondary Outcome Measures:

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) ]
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) ]
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) ]
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) ]
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) ]
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) ]
Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: Baseline up to 53 months ]
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) ]
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) ]
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)
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) ]
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)
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) ]


Estimated Enrollment:	900
Actual Study Start Date:	June 23, 2015
Estimated Study Completion Date:	April 30, 2020
Estimated Primary Completion Date:	April 30, 2020 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Atezolizumab Plus Nab-Paclitaxel Participants 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.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody Atezolizumab at a fixed dose of 840 milligrams via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, symptomatic deterioration attributed to disease progression, or death. Other Name: Tecentriq, MPDL3280A Drug: Nab-Paclitaxel Nab-Paclitaxel at a starting dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle. Nab-Paclitaxel will be administered for a target of at least 6 cycles, with no maximum in the absence of disease progression or unacceptable toxicity. Other Name: Abraxane®
Placebo Comparator: Placebo Plus Nab-Paclitaxel Participants 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.	Drug: Nab-Paclitaxel Nab-Paclitaxel at a starting dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle. Nab-Paclitaxel will be administered for a target of at least 6 cycles, with no maximum in the absence of disease progression or unacceptable toxicity. Other Name: Abraxane® Drug: Placebo Placebo administered via IV infusion on Days 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, symptomatic deterioration attributed to disease progression, or death.

Arms

Assigned Interventions

Experimental: Atezolizumab Plus Nab-Paclitaxel

Participants 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.

Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody

Atezolizumab at a fixed dose of 840 milligrams via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, symptomatic deterioration attributed to disease progression, or death.

Other Name: Tecentriq, MPDL3280A

Drug: Nab-Paclitaxel

Nab-Paclitaxel at a starting dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle. Nab-Paclitaxel will be administered for a target of at least 6 cycles, with no maximum in the absence of disease progression or unacceptable toxicity.

Other Name: Abraxane®

Placebo Comparator: Placebo Plus Nab-Paclitaxel

Participants 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.

Drug: Nab-Paclitaxel

Nab-Paclitaxel at a starting dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle. Nab-Paclitaxel will be administered for a target of at least 6 cycles, with no maximum in the absence of disease progression or unacceptable toxicity.

Other Name: Abraxane®

Drug: Placebo

Placebo administered via IV infusion on Days 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, symptomatic deterioration attributed to disease progression, or death.

Eligibility


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

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

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02425891

Contacts


Contact: Reference Study ID Number: WO29522 www.roche.com/about_roche/roche_worldwide.htm	888-662-6728 (U.S. and Canada)	global-roche-genentech-trials@gene.com

Show 318 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information


Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT02425891 History of Changes
Other Study ID Numbers:	WO29522 2014-005490-37 ( EudraCT Number )
Study First Received:	April 21, 2015
Last Updated:	July 7, 2017

Additional relevant MeSH terms:


Breast Neoplasms Triple Negative Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel 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

ClinicalTrials.gov processed this record on July 14, 2017