Clinical trial NCT03262935: SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer
Official title: A Multi-centre, Open-label, Randomized Clinical Trial Comparing the Efficacy and Safety of the Antibody-drug Conjugate SYD985 to Physician's Choice in Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Lead sponsor: Byondis B.V.
Sponsor class: INDUSTRY
First posted: 2017-08-25
Enrollment: 437
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to demonstrate that SYD985 \[(vic-)trastuzumab duocarmazine\] is superior to physician's choice in prolonging progression free survival.

Detailed description: This study is designed as a randomized, active-controlled, superiority study in patients with unresectable locally advanced or metastatic HER2-positive breast cancer. The patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment.

Eligible patients will be randomly assigned (2:1) to receive SYD985 or physician's choice treatment until disease progression, unacceptable toxicity or study termination by the Sponsor. During treatment, patients will have to visit the clinical site to assess efficacy, quality of life (QoL), and safety using standardized criteria.

Eligibility criteria: Main Inclusion Criteria:

* Female patients with histologically-confirmed, unresectable locally advanced or metastatic breast cancer;
* Patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment for locally advanced or metastatic disease;
* HER2-positive tumor status;
* Patients must have measurable or non-measurable disease that is evaluable per RECIST 1.1;
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
* Estimated life expectancy \> 12 weeks at randomization;
* Adequate organ function and blood cell counts.

Main Exclusion Criteria:

* Current or previous use of a prohibited medication as listed in the protocol;
* History of infusion-related reactions and/or hypersensitivity to trastuzumab, (ado-)trastuzumab emtansine;
* History of keratitis;
* Severe, uncontrolled systemic disease at screening;
* Left Ventricular Ejection Fraction (LVEF) \< 50%, or a history of clinically significant decrease in LVEF during previous treatment with trastuzumab or (ado-)trastuzumab emtansine;
* Cardiac troponin value above the Upper Limit of Normal (ULN);
* History of clinically significant cardiovascular disease;
* Untreated brain metastases, symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to randomization;
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.

Primary outcomes:
measure: Progression Free Survival
timeFrame: baseline until primary analysis data cut-off date of 31March2021
Secondary outcomes:
measure: Overall Survival
timeFrame: baseline until final Overall Survival analysis data cut-off date of 30June2022
measure: Objective Response Rate
timeFrame: baseline until primary analysis data cut-off date of 31March2021
measure: Investigator Assessed Progression Free Survival
timeFrame: baseline until primary analysis data cut-off date of 31March2021
measure: Patient Reported Outcomes for Health Related Quality of Life
timeFrame: baseline until primary analysis data cut-off date of 31March2021
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Southern Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: San Diego
country: United States
facility: Moores UCSD Cancer Center
state: California
city: Pensacola
country: United States
facility: Woodlands Medical Specialists
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Pinehurst
country: United States
facility: FirstHealth Outpatient Cancer Center
state: North Carolina
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists
state: Oregon
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMS
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Oncology PA (Texas Oncology-Dallas Presbyterian Hospital)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology- Baylor Charles A. Sammor
state: Texas
city: Denton
country: United States
facility: Texas Oncology - Denton South
state: Texas
city: Houston
country: United States
facility: Texas Oncology-Memorial City
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio Northeast
state: Texas
city: Tyler
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Brussel
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: University Hospital Antwerp
city: Gent
country: Belgium
facility: UZ Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven - campus Gasthuisberg
city: Liege
country: Belgium
facility: CHU Liege
city: Edmonton
country: Canada
facility: Cross Cancer Institute
city: Kelowna
country: Canada
facility: BC Cancer Agency Centre for the Southern Interior
city: Montreal
country: Canada
facility: McGill University Health Centre
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Center
city: Naestved
country: Denmark
facility: Sealand University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Sønderborg
country: Denmark
facility: Sønderborg sygehus
city: Angers
country: France
facility: Institut de Cancerologie de l'ouest
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bourg-en-Bresse
country: France
facility: CH Fleyrait
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Lyon Sud
city: Dijon
country: France
facility: Centre Georges francois leclerc
city: Lille
country: France
facility: Oscar Lambret
city: Metz
country: France
facility: CHR Metz-Thionville
city: Nantes
country: France
facility: Hopital Prive du Confluent
city: Paris
country: France
facility: Hopital Saint Louis
city: Pierre-Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Centre Henri Becquere
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Bari
country: Italy
facility: IRCCS Istituto Oncologico
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi
city: Catania
country: Italy
facility: Azienda Ospedaliera Garibaldi- Nesima
city: Firenze
country: Italy
facility: Azienda Ospedaliero - Universitaria Careggi
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Modena
country: Italy
facility: University Hospital of Modena
city: Monza
country: Italy
facility: Ospedale San Gerardo-Asst Monza
city: Padova
country: Italy
facility: Istituto Oncologico Veneto Irccs
city: Prato
country: Italy
facility: Nuovo Ospedale Santo Stefano
city: Roma
country: Italy
facility: Istituto Nazionale dei Tumori Regina Elena
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo Della Sofferenza
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Amsterdam
country: Netherlands
facility: VU Medical Center
state: Noord-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Singapore
country: Singapore
facility: National University Cancer Institute
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Quironsalud
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron Vall d' Hebron Institute of Oncology (VHIO)
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Institut Catala D'oncologia
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: IOB del Hospital Ruber Internacional
city: Madrid
country: Spain
facility: Hospital HM Universitario Sanchinarro
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Gävle
country: Sweden
facility: Gävle Sjukhus Onkologkliniken
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Karolina University Hospital
city: Uppsala
country: Sweden
facility: Akademiska Hospital
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre VCC
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: SCRI UK
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation
city: Oxford
country: United Kingdom
facility: Oxford University NHS hospital
Study officials:
affiliation: Byondis B.V., The Netherlands
name: Evelyn van den Tweel, PhD
role: STUDY_DIRECTOR
References: