Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02924883
Other study ID # WO30085
Secondary ID 2015-004189-27
Status Completed
Phase Phase 2
First received
Last updated
Start date September 26, 2016
Est. completion date February 6, 2020

Study information

Verified date January 2021
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This Phase II, double-blind, randomized, placebo-controlled multicenter study will investigate the efficacy and safety of trastuzumab emtansine in combination with atezolizumab or atezolizumab-placebo in participants with HER2-positive locally advanced or metastatic BC who have received prior trastuzumab and taxane based therapy, either alone or in combination, and/or who have progressed within 6 months after completing adjuvant therapy.


Recruitment information / eligibility

Status Completed
Enrollment 202
Est. completion date February 6, 2020
Est. primary completion date December 11, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Archival tumor samples must be obtained from primary and/or metastatic sites - Able to submit tumor tissue that is evaluable for programmed death- ligand 1 (PD-L1) expression - HER-2 positive BC as defined by an immunohistochemistry score of 3 or gene amplified by in-situ hybridization as defined by a ratio of greater than or equal to (>=) 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies - Histologically or cytologically confirmed invasive BC: incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic BC - Prior treatment for BC in the: adjuvant; unresectable locally advanced; or metastatic settings; which must include both, a taxane and trastuzumab (alone or in combination with another agent) - Progression must have occurred during or after most recent treatment for locally advanced/metastatic BC or within 6 months after completing adjuvant therapy - Participants must have measurable disease that is evaluable as per RECIST v1.1 - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women and for women less than 12 months after the onset of menopause - Use of highly effective method of contraception as defined by the protocol Exclusion Criteria: - Prior treatment with trastuzumab emtansine, cluster of differentiation 137 agonists, anti-programmed death-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents - Receipt of any anti-cancer drug/biologic or investigational treatment within 21 days prior to Cycle 1 Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1 Day 1; recovery of treatment related toxicity consistent with other eligibility criteria - Radiation therapy within 2 weeks prior to Cycle 1, Day 1 - History of exposure to the cumulative doses of anthracyclines - History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or participants who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence - Cardiopulmonary dysfunction, symptomatic pleural effusion, pericardial effusion, or ascites - Participants with severe infection within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia - Current severe, uncontrolled systemic disease - Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment - Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, sclerosis cholangitis or active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus - Need for current chronic corticosteroid therapy (>=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids) - 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 greater than (>) 2 weeks prior to randomization - Participants with known central nervous system disease - Leptomeningeal disease - History of autoimmune disease - Prior allogeneic stem cell or solid organ transplantation - Active tuberculosis - Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study - Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization - Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial - Participants who are breastfeeding, or intending to become pregnant during the study

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Atezolizumab
Atezolizumab 1200 mg IV infusion
Trastuzumab emtansine
Trastuzumab emtansine 3.6 mg/kg IV infusion
Other:
Placebo
Placebo matched to atezolizumab

Locations

Country Name City State
Australia Peter MacCallum Cancer Center East Melbourne Victoria
Australia Peninsula and South Eastern Haematology and Oncology Group Frankston Victoria
Australia St George Hospital; Cancer Care Centre Kogarah New South Wales
Australia Sunshine Hospital St Albans Victoria
Australia St John of God Hospital; Bendat Cancer Centre Subiaco Western Australia
Australia Calvary Mater Newcastle Waratah New South Wales
Australia Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology Woolloongabba Queensland
Canada McGill University; Glen Site; Oncology Montreal Quebec
Canada McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology Montreal Quebec
Canada Lakeridge Health Oshawa; Oncology Oshawa Ontario
Canada The Ottawa Hospital Cancer Centre; Oncology Ottawa Ontario
Canada Hopital du Saint Sacrement Quebec City Quebec
Canada Sunnybrook Odette Cancer Centre Toronto Ontario
Germany HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe Berlin
Germany Studienzentrum Berlin City Berlin
Germany Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum Essen
Germany Praxis für Interdisziplinäre Onkologie und Hämatologie GbR Freiburg
Germany Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg Heidelberg
Germany Institut für Versorgungsforschung in der Onkologie GbR Koblenz Koblenz
Italy Centro Di Riferimento Oncologico; SOC Oncologia Medica C Aviano Friuli-Venezia Giulia
Italy A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2 Bologna Emilia-Romagna
Italy Centro Catanese Di Oncologia; Oncologia Medica Catania Sicilia
Italy IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A Napoli Campania
Italy Ospedale Regionale Di Parma; Divisione Di Oncologia Medica Parma Emilia-Romagna
Italy Ospedale Santo Stefano, Azienda USL Centro Prato Prato Toscana
Korea, Republic of National Cancer Center Goyang-si
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul
Spain Hospital Univ Vall d'Hebron; Servicio de Oncologia Barcelona
Spain Hospital Universitario Reina Sofia; Servicio de Oncologia Córdoba Cordoba
Spain Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología La Coruña
Spain Hospital Ramon y Cajal; Servicio de Oncologia Madrid
Spain Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia Valencia
Spain Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia Valencia
Taiwan Changhua Christian Hospital; Dept of Surgery Changhua
Taiwan Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery Kaohsiung
Taiwan China Medical University Hospital; Surgery Taichung
Taiwan Chi-Mei Medical Center Tainan
Taiwan National Taiwan Uni Hospital; General Surgery Taipei
Taiwan VETERANS GENERAL HOSPITAL; Department of General Surgery Taipei
Taiwan Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology Taipei City
Taiwan Chang Gung Memorial Hospital - Linkou Taoyuan
United Kingdom Royal United Hospital; Oncology Department Bath
United Kingdom Beatson West of Scotland Cancer Centre Glasgow
United Kingdom Royal Free Hospital; Dept of Oncology London
United Kingdom Royal Marsden Hosp NHS Fnd; Breast Unit London
United Kingdom Christie Hospital; Breast Cancer Research Office Manchester
United Kingdom Nottingham City Hospital Nottingham
United Kingdom Weston Park Hospital; Cancer Clinical Trials Centre Sheffield
United Kingdom Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit Sutton
United Kingdom Singleton Hospital; Pharmacy Swansea
United States Northside Hospital Atlanta Georgia
United States University of Colorado Aurora Colorado
United States Johns Hopkins Univ Med Center Baltimore Maryland
United States SCRI Tennessee Oncology Chattanooga Chattanooga Tennessee
United States Ohio State Uni Medical Center Columbus Ohio
United States San Juan Oncology Associates Farmington New Mexico
United States SCRI Florida Cancer Specialists South Fort Myers Florida
United States Tennessee Oncology; Sarah Cannon Research Institute Nashville Tennessee
United States Laura and ISAAC Perlmutter Cancer Center at NYU Langone. New York New York
United States Breastlink Med Group Inc Orange California
United States Magee Womens Hospital Pittsburgh Pennsylvania
United States Florida Cancer Specialists; Saint Petersburg Saint Petersburg Florida
United States University of Washington Seattle Washington
United States MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center) Washington District of Columbia
United States Cancer Care Associates of York York Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Italy,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-Free Survival (PFS) as Determined by Investigator's Tumor Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions. Baseline up to approximately 15 months
Primary Percentage of Participants With Adverse Events An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Baseline up to study completion, approximately 40 months
Secondary Overall Survival (OS) OS was defined as the time from randomization to death from any cause. Baseline up to study completion or death, whichever occurs first, approximately 40 months
Secondary Percentage of Participants With Objective Response (OR) as Determined by Investigator's Tumor Assessment Using RECIST v1.1 An OR was defined as a complete or partial response determined on 2 consecutive occasions = 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders. Baseline up to approximately 15 months
Secondary Duration of OR as Determined by Investigator's Tumor Assessment Using RECIST v1.1 Duration of OR was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first. Baseline up to approximately 15 months
Secondary Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine Average post infusion Trastuzumab Emtansine concentration Pre-infusion (0 hour [h]), 30 minutes (min) after end of infusion (EOI) (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days); at any time during study treatment/early discontinuation visit (approx. 40 months)
Secondary Cmax of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) Average post infusion Deacetyl Mercapto 1-Oxopropyl Maytansine concentration of trastuzumab emtansine infusion Pre-infusion (0 h) on Day 1 Cycle 1 and 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4 (each cycle = 21 days)
Secondary Cmax of Total Trastuzumab Pre-infusion (0 h), 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days)
Secondary Cmax of Atezolizumab Average post infusion atezolizumab concentration Pre-infusion (0 h), 30 min after EOI (over 60 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycles 2, 3, 8, and every 8 cycles thereafter (each cycle=21 days) up to 120 days after treatment completion/early discontinuation (approx. 40 months)
Secondary Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to Atezolizumab ATAs are antibodies that inactivate the therapeutic effects of Atezolizumab. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., = 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response). Pre-infusion (0 h) on Day 1 Cycles 1, 2, 3, 4, 8, and every 8 cycles thereafter (each cycle = 21 days) up to 120 days after treatment completion or early discontinuation (approximately 40 months)
Secondary Percentage of Participants With ATAs to Trastuzumab Emtansine ATAs are antibodies that inactivate the therapeutic effects of Trastuzumab Emtansine. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., = 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response). Pre-infusion (0 h) on Day 1 Cycles 1 and 4 (each cycle = 21 days); and at any time during study treatment/early discontinuation visit (approximately 40 months)
See also
  Status Clinical Trial Phase
Withdrawn NCT04872608 - A Study of Letrozole, Palbociclib, and Onapristone ER in People With Metastatic Breast Cancer Phase 1
Terminated NCT02202746 - A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer Phase 2
Completed NCT02506556 - Phosphatidylinositol 3-kinase (PI3K) Alpha iNhibition In Advanced Breast Cancer Phase 2
Recruiting NCT05534438 - A Study on Adding Precisely Targeted Radiation Therapy (Stereotactic Body Radiation Therapy) to the Usual Treatment Approach (Drug Therapy) in People With Breast Cancer Phase 2
Recruiting NCT03368729 - Niraparib in Combination With Trastuzumab in Metastatic HER2+ Breast Cancer Phase 1/Phase 2
Completed NCT04103853 - Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer Phase 1
Terminated NCT01847599 - Educational Intervention to Adherence of Patients Treated by Capecitabine +/- Lapatinib N/A
Active, not recruiting NCT03147287 - Palbociclib After CDK and Endocrine Therapy (PACE) Phase 2
Not yet recruiting NCT06062498 - Elacestrant vs Elacestrant Plus a CDK4/6 Inhibitor in Patients With ERpositive/HER2-negative Advanced or Metastatic Breast Cancer Phase 2
Recruiting NCT05383196 - Onvansertib + Paclitaxel In TNBC Phase 1/Phase 2
Recruiting NCT04095390 - A Phase Ⅱ Trial of Pyrotinib Combination With CDK4/6 Inhibitor SHR6390 in Patients Prior Trastuzumab-treated Advanced HER2-Positive Breast Cancer Phase 2
Active, not recruiting NCT04432454 - Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation Phase 2
Recruiting NCT03323346 - Phase II Trial of Disulfiram With Copper in Metastatic Breast Cancer Phase 2
Recruiting NCT05744375 - Trastuzumab Deruxtecan in First-line HER2-positive Locally Advanced/MBC Patients Resistant to Trastuzumab+Pertuzumab Phase 2
Completed NCT01942135 - Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3) Phase 3
Completed NCT01881230 - Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer) Phase 2/Phase 3
Active, not recruiting NCT04448886 - Sacituzumab Govitecan +/- Pembrolizumab In HR+ / HER2 - MBC Phase 2
Completed NCT01401959 - Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy Phase 2
Terminated NCT04720664 - Oral SM-88 in Patients With Metastatic HR+/HER2- Breast Cancer Phase 2
Withdrawn NCT05191004 - Study of NUV-422 in Combination With Fulvestrant in Patients With HR+HER2- aBC Phase 1/Phase 2