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

NCT ID: NCT03262935

Last Updated: 2023-10-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

437 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-15

Study Completion Date

2022-06-30

Brief Summary

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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

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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.

Conditions

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Metastatic Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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(vic-)trastuzumab duocarmazine

SYD985, every 3 weeks (Q3W)

Group Type EXPERIMENTAL

(vic-)trastuzumab duocarmazine

Intervention Type DRUG

Intravenous SYD985, Q3W

Physician's choice

1. Lap/Cap
2. T/Cap
3. T/Vino
4. T/Eri

Group Type ACTIVE_COMPARATOR

Physician's choice

Intervention Type DRUG

See drug label

Interventions

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(vic-)trastuzumab duocarmazine

Intravenous SYD985, Q3W

Intervention Type DRUG

Physician's choice

See drug label

Intervention Type DRUG

Other Intervention Names

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SYD985 Trastuzumab vc-seco-DUBA Lapatinib (Lap) Capecitabine (Cap) Trastuzumab (T) Vinorelbine (Vino) Eribulin (Eri)

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Byondis B.V.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Evelyn van den Tweel, PhD

Role: STUDY_DIRECTOR

Byondis B.V., The Netherlands

Locations

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Southern Cancer Center

Mobile, Alabama, United States

Site Status

Arizona Clinical Research Center

Tucson, Arizona, United States

Site Status

Moores UCSD Cancer Center

San Diego, California, United States

Site Status

Woodlands Medical Specialists

Pensacola, Florida, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Cancer Center of Kansas

Wichita, Kansas, United States

Site Status

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Site Status

FirstHealth Outpatient Cancer Center

Pinehurst, North Carolina, United States

Site Status

Toledo Clinic Cancer Center

Toledo, Ohio, United States

Site Status

Northwest Cancer Specialists

Portland, Oregon, United States

Site Status

Magee-Womens Hospital of UPMS

Pittsburgh, Pennsylvania, United States

Site Status

Texas Oncology PA (Texas Oncology-Dallas Presbyterian Hospital)

Dallas, Texas, United States

Site Status

Texas Oncology- Baylor Charles A. Sammor

Dallas, Texas, United States

Site Status

Texas Oncology - Denton South

Denton, Texas, United States

Site Status

Texas Oncology-Memorial City

Houston, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Texas Oncology-San Antonio Northeast

San Antonio, Texas, United States

Site Status

Texas Oncology-Tyler

Tyler, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

University Hospital Antwerp

Edegem, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

AZ Groeninge

Kortrijk, , Belgium

Site Status

UZ Leuven - campus Gasthuisberg

Leuven, , Belgium

Site Status

CHU Liege

Liège, , Belgium

Site Status

Cross Cancer Institute

Edmonton, , Canada

Site Status

BC Cancer Agency Centre for the Southern Interior

Kelowna, , Canada

Site Status

McGill University Health Centre

Montreal, , Canada

Site Status

The Ottawa Hospital Cancer Center

Ottawa, , Canada

Site Status

Sealand University Hospital

Næstved, , Denmark

Site Status

Odense University Hospital

Odense, , Denmark

Site Status

Sønderborg sygehus

Sønderborg, , Denmark

Site Status

Institut de Cancerologie de l'ouest

Angers, , France

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

CH Fleyrait

Bourg-en-Bresse, , France

Site Status

Centre Hospitalier Lyon Sud

Corbeil-Essonnes, , France

Site Status

Centre Georges francois leclerc

Dijon, , France

Site Status

Oscar Lambret

Lille, , France

Site Status

CHR Metz-Thionville

Metz, , France

Site Status

Hopital Prive du Confluent

Nantes, , France

Site Status

Hopital Saint Louis

Paris, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Centre Henri Becquere

Rouen, , France

Site Status

Centre Paul Strauss

Strasbourg, , France

Site Status

IRCCS Istituto Oncologico

Bari, , Italy

Site Status

Policlinico S.Orsola-Malpighi

Bologna, , Italy

Site Status

Azienda Ospedaliera Garibaldi- Nesima

Catania, , Italy

Site Status

Azienda Ospedaliero - Universitaria Careggi

Florence, , Italy

Site Status

IRCCS Ospedale San Raffaele

Milan, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

Istituto Europeo di Oncologia

Milan, , Italy

Site Status

University Hospital of Modena

Modena, , Italy

Site Status

Ospedale San Gerardo-Asst Monza

Monza, , Italy

Site Status

Istituto Oncologico Veneto Irccs

Padua, , Italy

Site Status

Nuovo Ospedale Santo Stefano

Prato, , Italy

Site Status

Istituto Nazionale dei Tumori Regina Elena

Roma, , Italy

Site Status

Azienda Ospedaliera Sant'Andrea

Roma, , Italy

Site Status

Casa Sollievo Della Sofferenza

San Giovanni Rotondo, , Italy

Site Status

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Site Status

VU Medical Center

Amsterdam, North Holland, Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

National University Cancer Institute

Singapore, , Singapore

Site Status

National Cancer Centre Singapore

Singapore, , Singapore

Site Status

Hospital General Universitario de Alicante

Alicante, , Spain

Site Status

Hospital Quironsalud

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron Vall d' Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Institut Catala D'oncologia

Barcelona, , Spain

Site Status

Hospital Arnau de Vilanova

Lleida, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

IOB del Hospital Ruber Internacional

Madrid, , Spain

Site Status

Hospital HM Universitario Sanchinarro

Madrid, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Gävle Sjukhus Onkologkliniken

Gävle, , Sweden

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Karolina University Hospital

Stockholm, , Sweden

Site Status

Akademiska Hospital

Uppsala, , Sweden

Site Status

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, , United Kingdom

Site Status

Velindre Cancer Centre VCC

Cardiff, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status

SCRI UK

London, , United Kingdom

Site Status

The Christie NHS Foundation

Manchester, , United Kingdom

Site Status

Oxford University NHS hospital

Oxford, , United Kingdom

Site Status

Countries

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

References

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Turner N, Saura C, Aftimos P, van den Tweel E, Oesterholt M, Koper N, Colleoni M, Kaczmarek E, Punie K, Song X, Armstrong A, Bianchi G, Stradella A, Ladoire S, Lim JSJ, Quenel-Tueux N, Tan TJ, Escriva-de-Romani S, O'Shaughnessy J; TULIP Trial Investigators. Trastuzumab Duocarmazine in Pretreated Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Breast Cancer: An Open-Label, Randomized, Phase III Trial (TULIP). J Clin Oncol. 2025 Feb 10;43(5):513-523. doi: 10.1200/JCO.24.00529. Epub 2024 Oct 23.

Reference Type DERIVED
PMID: 39442070 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SYD985.002

Identifier Type: -

Identifier Source: org_study_id

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