SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

— TULIP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03262935
• Other study ID #: SYD985.002
• Status: Completed
• Phase: Phase 3
• Start date: December 15, 2017
• Est. completion date: June 30, 2022

Study information

• Verified date: June 2023
• Source: Byondis B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 437
• Est. completion date: June 30, 2022
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• (vic-)trastuzumab duocarmazine
Intravenous SYD985, Q3W
• Physician's choice
See drug label

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Byondis B.V.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  France,  Italy,  Netherlands,  Singapore,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by central assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred earlier.	baseline until primary analysis data cut-off date of 31March2021
Secondary	Overall Survival	Overall survival is defined as the time from date of randomization to death due to any cause.	baseline until final Overall Survival analysis data cut-off date of 30June2022
Secondary	Objective Response Rate	Objective Response Rate is defined as the proportion of patients with a centrally assessed best overall response of complete response or partial response according to RECIST v1.1.	baseline until primary analysis data cut-off date of 31March2021
Secondary	Investigator Assessed Progression Free Survival	Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by investigator assessment according to RECIST v1.1 or death due to any cause, whichever occurred earlier.	baseline until primary analysis data cut-off date of 31March2021
Secondary	Patient Reported Outcomes for Health Related Quality of Life	Change in the global health status/Quality of Life (QoL) scale score of the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire C30 from baseline (cycle 1). The raw score (1 to 7) has been transformed to a score ranging from 0 to 100. A higher score means a better outcome: hence a positive change from baseline means an improvement in global health status/Quality of Life and a negative change from baseline means a worsening of global health status/Quality of Life.	baseline until primary analysis data cut-off date of 31March2021