Clinical trial • Phase II • Oncology

TRASTUZUMAB for HER2-positive locally advanced or metastatic breast cancer

Phase II trial of TRASTUZUMAB for HER2-positive locally advanced or metastatic breast cancer. 282 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
HER2-positive locally advanced or metastatic breast cancer
Trial Stage
Phase II
Drug Modality
Monoclonal antibody|ADC

Key dates

Initial CTIS Submission Date
10-07-2024
First CTIS Authorization Date
17-10-2024

Trial design

Phase II trial across 41 sites in France.

Biomarker Stratified
True, biomarker: ctDNA (circulating tumor DNA); strata: ctDNA negative at baseline vs ctDNA positive at baseline
Target Sample Size
282
Trial Duration For Participant
1095

Eligibility

Recruits 282 Patients must sign written informed consent. When the patient is physically unable to give written consent, a trusted person of their choice, independent from the investigator or the sponsor, can sign the patient's consent. Persons deprived of their liberty or under protective custody or guardianship are excluded..

Pregnancy Exclusion
Pregnant women or women who are breast-feeding
Vulnerable Population
Patients must sign written informed consent. When the patient is physically unable to give written consent, a trusted person of their choice, independent from the investigator or the sponsor, can sign the patient's consent. Persons deprived of their liberty or under protective custody or guardianship are excluded.

Inclusion criteria

  • {"criterion_text":"- Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient’s consent;\n- Adequate cardiac, renal, haematological and hepatic functions according to guidelines hospital;\n- Women of childbearing potential must have a negative serum or urine pregnancy test done within 28 days before inclusion;\n- Non post-menopausal women and fertile men must agree to use adequate contraception methods during the study. Hormonal contraceptives such as birth control pills, patches, implants, or injections are not allowed in patients who are hormone receptor positive\n- Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan and other study procedures including follow-up;\n- Patients must be affiliated to a Social Security System (or equivalent).\n- Men or women ≥ 18 years of age;\n- Documented diagnosis of locally advanced inoperable or metastatic histologically-proven HER2-positive breast cancer (HER2-positive is defined as HER2 3+ immunohistochemical overexpression, or the presence of HER2 amplification, according to ASCO-CAP guidelines);\n- Must have an adequate archival tumor tissue sample available for centralized WES analysis to design the ctDNA test. Requirements: • Sample age: Less than 10 years old. • Preferred sample types (in order of priority): a. Most recent resected tumor tissue sample b. Affected lymph node with adequate cellularity.\n- Patient with ECOG Performance Status (PS) ≤1;\n- Patient must have received continuous anti-HER2 targeted therapy (including Trastuzumab, Trastuzumab/Pertuzumab, Trastuzumab-Deruxtecan or T-DM1) treatment for at least 2 years in any line setting, for their locally advanced inoperable ormetastatic HER2 + breast cancer (prior treatment interruption of 3 months maximum is allowed), with complete response or partial response at last radiological assessment;\n- In case of bone disease only, complete metabolic response in 18-FDG pet-scanner is required at screening;\n- Patient with treated (surgery and/or radiation therapy) and controlled primary tumor;\n- Patients with ER-positive disease may or may not have received concomitant endocrine therapy (which must be continued if present). Concomitant ovarian blockade using LHRH agonists is authorised as well;"}

Exclusion criteria

  • {"criterion_text":"- Any breast cancer progression over the past 2 years or at study entry;\n- Participation in another clinical study whose procedures interfere with those of the study (within 28 days prior to patient enrolment and for the duration of the study);\n- Persons deprived of their liberty or under protective custody or guardianship.\n- Patient concurrently using other approved or investigational antineoplastic agents than trastuzumab, pertuzumab, Trastuzumab-Deruxtecan, TDM-1 +/- endocrine therapy;\n- Had an history of tumoral meningitis or clinically active central nervous system metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms; a. Subjects with curatively treated brain metastases (i.e., complete removal surgery or stereotactic radiotherapy) who are no longer symptomatic and do not require treatment with corticosteroids or anticonvulsants may be included in the study provided they have recovered from the acute toxicity of radiotherapy and there has been no progression of the brain metastases within the past 24 months. b. Subjects with brain metastases only or treated with whole brain radiotherapy will be excluded of the study\n- Major concurrent disease affecting cardiovascular system, liver, kidneys, haematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient’s participation in this trial or would likely interfere with study procedures or results;\n- History of any prior ipsi or contralateral breast cancer (except in case of DCIS) unless if both primary tumors were confirmed to be HER2-positive\n- Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease and treatment for at least 3 years;\n- Major surgery within 2 weeks prior to study entry\n- Pregnant women or women who are breast-feeding\n- Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The progression-free rate (PFR) defined by radiological, and/or molecular progression. The PFR is defined as the time from the date of registration to the date of the first documented event among radiological progressions (RECIST 1.1), molecular progressions defined by ctDNA+, or death due to any cause, whichever occurs first. Patients alive without any of these events will be censored.","definition_or_measurement_approach":"PFR measured as time from date of registration to first documented radiological progression (RECIST 1.1), molecular progression defined by ctDNA positivity, or death; patients without events censored."}

Secondary endpoints

  • {"endpoint_text":"- Efficacy : PFS will be defined as the time from the date of registration to the date of the first documented cancer progression measured by RECIST 1.1 or death due to any cause, whichever occurs first. Patients alive without progression will be censored.\n- Efficacy : The ctDNA dynamics is defined as changes in the level of ctDNA (from negative to positive) during the surveillance phase. Positivity rate is defined as the proportion of patients with positive ctDNA.\n- Efficacy : OS will be defined as the time from the date of registration to the date of death due to any cause.\n- Efficacy : Molecular response is defined as the percentage of patients who reached molecular remission (ctDNA clearance) 3 months after reintroduction of anti-HER2 treatment among patients with ctDNA positive without RECIST progression.\n- Efficacy : Objective Response Rate (ORR), defined as the number of patients with at least a confirmed complete response (CR) or partial response (PR) to reintroduction of anti-HER2 treatment, among patients with RECIST progression during the surveillance phase\n- Efficacy : Duration of Response (Dor) is defined, among patients with RECIST progression during the surveillance phase, as the time from the onset of response after reintroduction of anti-HER2 treatment, to progression or death due to any cause, whichever occurs first.\n- Quality of Life : QoL will be assessed using the EORTC QLQ-C30 and QLQ-BR45 questionnaire\n- Quality of life : Anxiety will be assessed by the STAI-state questionnaire\n- Quality of life : Decision regret will be assessed by the decision regret scale","definition_or_measurement_approach":"PFS: time from registration to documented progression by RECIST 1.1 or death (censored if alive without progression). ctDNA dynamics: change from ctDNA negative to positive during surveillance; positivity rate = proportion with positive ctDNA. OS: time from registration to death. Molecular response: proportion achieving ctDNA clearance 3 months after anti-HER2 reintroduction among ctDNA-positive without RECIST progression. ORR: confirmed CR or PR after reintroduction among those with RECIST progression. DoR: time from response onset after reintroduction to progression or death. QoL: measured with EORTC QLQ-C30 and QLQ-BR45. Anxiety: STAI-state questionnaire. Decision regret: decision regret scale."}

Recruitment

Planned Sample Size
282
Recruitment Window Months
60
Consent Approach
Patients must sign a written informed consent prior to any trial-specific procedures. When a patient is physically unable to provide written consent, a trusted person of their choice, independent from the investigator or sponsor, may sign the patient's consent. No paediatric assent procedures are described (inclusion requires age ≥ 18). Subject information and informed consent form documents are listed in the application.

Geography

Total Number Of Sites
41
Total Number Of Participants
282

France

Earliest CTIS Part Ii Submission Date
18-09-2024
Latest Decision Or Authorization Date
18-02-2026
Processing Time Days
518
Number Of Sites
41
Number Of Participants
282

Sites

Site Name
Institut Curie
Department Name
Oncologie
Principal Investigator Name
Diana BELLO-ROUFAI
Principal Investigator Email
diana.belloroufai@curie.fr
Contact Person Name
Diana BELLO-ROUFAI
Contact Person Email
diana.belloroufai@curie.fr
Site Name
Polyclinique Saint-Come
Department Name
Oncologie
Principal Investigator Name
KaÏs ALDABBAGH
Principal Investigator Email
kais.aldabbagh@stcome.com
Contact Person Name
KaÏs ALDABBAGH
Contact Person Email
kais.aldabbagh@stcome.com
Site Name
Centre Jean Perrin
Department Name
Oncologie
Principal Investigator Name
Marie-Ange MOURET-REYNIER
Contact Person Name
Marie-Ange MOURET-REYNIER
Site Name
Centre Hospitalier Intercommunal De Frejus-Saint-Raphaeel
Department Name
Oncologie
Principal Investigator Name
Jean Francois PAITEL
Contact Person Name
Jean Francois PAITEL
Site Name
Sainte Catherine Institut Du Cancer Avignon-Provence
Department Name
Oncologie
Principal Investigator Name
Julien GRENIER
Principal Investigator Email
j.grenier@isc84.org
Contact Person Name
Julien GRENIER
Contact Person Email
j.grenier@isc84.org
Site Name
Institut Godinot
Department Name
Oncologie
Principal Investigator Name
Christelle JOUANNAUD
Principal Investigator Email
christelle.jouannaud@reims.unicancer.fr
Contact Person Name
Christelle JOUANNAUD
Site Name
Centre Hospitalier De Bourg-En-Bresse
Department Name
Oncologie
Principal Investigator Name
Patrick ARNAUD-COFFIN
Principal Investigator Email
parnaudcoffin@ch-bourg01.fr
Contact Person Name
Patrick ARNAUD-COFFIN
Contact Person Email
parnaudcoffin@ch-bourg01.fr
Site Name
Institut Bergonie
Department Name
Oncologie
Principal Investigator Name
Monica ARNEDOS
Principal Investigator Email
m.arnedos@bordeaux.unicancer.fr
Contact Person Name
Monica ARNEDOS
Site Name
Institut de Cancérologie du Gard
Department Name
Oncologie
Principal Investigator Name
Frederic FITENI
Principal Investigator Email
frederic.fiteni@chu-nimes.fr
Contact Person Name
Frederic FITENI
Contact Person Email
frederic.fiteni@chu-nimes.fr
Site Name
Pole Sante Republique
Department Name
Oncologie
Principal Investigator Name
Pierre DALLOZ
Principal Investigator Email
pdalloz@polesanterepublique.com
Contact Person Name
Pierre DALLOZ
Site Name
Hopital NOVO
Department Name
Oncologie
Principal Investigator Name
Rolande NGUEFACK
Principal Investigator Email
rolande.nguefack@ght-novo.fr
Contact Person Name
Rolande NGUEFACK
Contact Person Email
rolande.nguefack@ght-novo.fr
Site Name
Centre Antoine Lacassagne
Department Name
Oncologie
Principal Investigator Name
Caroline BAILLEUX
Principal Investigator Email
caroline.bailleux@nice.unicancer.fr
Contact Person Name
Caroline BAILLEUX
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Oncologie
Principal Investigator Name
Johanna WASSERMANN
Principal Investigator Email
johanna.wassermann@aphp.fr
Contact Person Name
Johanna WASSERMANN
Contact Person Email
johanna.wassermann@aphp.fr
Site Name
Institut De Cancerologie De Lorraine
Department Name
Oncologie
Principal Investigator Name
Camille SIMON
Principal Investigator Email
v.massard@nancy.unicancer.fr
Contact Person Name
Camille SIMON
Contact Person Email
v.massard@nancy.unicancer.fr
Site Name
Institut Paoli Calmettes
Department Name
Oncologie
Principal Investigator Name
Alexandre TASSIN DE NONNEVILLE
Principal Investigator Email
denonnevillea@pc.unicancer.fr
Contact Person Name
Alexandre TASSIN DE NONNEVILLE
Contact Person Email
denonnevillea@pc.unicancer.fr
Site Name
Centre Hospitalier De La Cote Basque
Department Name
Oncologie
Principal Investigator Name
Thomas GRELLETY
Principal Investigator Email
tgrellety@ch-cotebasque.fr
Contact Person Name
Thomas GRELLETY
Contact Person Email
tgrellety@ch-cotebasque.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Oncologie
Principal Investigator Name
Anne PATSOURIS
Principal Investigator Email
anne.patsouris@ico.unicancer.fr
Contact Person Name
Anne PATSOURIS
Site Name
Institut Régional Cancer Montpellier - ICM Val d'Aurelle
Department Name
Oncologie
Principal Investigator Name
Véronique D'HONDT
Principal Investigator Email
Veronique.Dhondt@icm.unicancer.fr
Contact Person Name
Véronique D'HONDT
Site Name
Centre Francois Baclesse
Department Name
Oncologie
Principal Investigator Name
George EMILE
Principal Investigator Email
g.emile@baclesse.unicancer.fr
Contact Person Name
George EMILE
Contact Person Email
g.emile@baclesse.unicancer.fr
Site Name
Oncopole Claudius Regaud
Department Name
Oncologie
Principal Investigator Name
Mony UNG
Principal Investigator Email
ung.mony@iuct-oncopole.fr
Contact Person Name
Mony UNG
Contact Person Email
ung.mony@iuct-oncopole.fr
Site Name
Clinique Tivoli Ducos
Department Name
Oncologie
Principal Investigator Name
Delphine GARBAY
Principal Investigator Email
d.garbay@tivoli-oncologie.fr
Contact Person Name
Delphine GARBAY
Contact Person Email
d.garbay@tivoli-oncologie.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Oncologie
Principal Investigator Name
Marie-Agnès BY
Principal Investigator Email
ma.by@chu-tours.fr
Contact Person Name
Marie-Agnès BY
Contact Person Email
ma.by@chu-tours.fr
Site Name
Centre Henri Becquerel
Department Name
Oncologie
Principal Investigator Name
Laetitia AUGUSTO
Principal Investigator Email
laetitia.augusto@chb.unicancer.fr
Contact Person Name
Laetitia AUGUSTO
Site Name
Centre De Lutte Contre Le Cancer Eugene Marquis
Department Name
Oncologie
Principal Investigator Name
Thibault DE LA MOTTE ROUGE
Principal Investigator Email
t.delamotterouge@rennes.unicancer.fr
Contact Person Name
Thibault DE LA MOTTE ROUGE
Site Name
Institut De Cancerologie Strasbourg Europe
Department Name
Oncologie
Principal Investigator Name
Carole PFLUMIO
Principal Investigator Email
c.pflumio@icans.eu
Contact Person Name
Carole PFLUMIO
Contact Person Email
c.pflumio@icans.eu
Site Name
Centre Hospitalier Simone Veil De Beauvais
Department Name
Oncologie
Principal Investigator Name
Hanifa AMMARGUELLAT
Principal Investigator Email
h.ammarguellat@ch-beauvais.fr
Contact Person Name
Hanifa AMMARGUELLAT
Contact Person Email
h.ammarguellat@ch-beauvais.fr
Site Name
Centre Hospitalier Annecy Genevois
Department Name
Oncologie
Principal Investigator Name
Charlotte BATAILLE-DEBUQUOY
Principal Investigator Email
cbatailledebuquoy@ch-annecygenevois.fr
Contact Person Name
Charlotte BATAILLE-DEBUQUOY
Site Name
L'Hopital Prive Du Confluent
Department Name
Oncologie
Principal Investigator Name
Dorothée CHOCTEAU
Principal Investigator Email
dorothee.chocteau@groupeconfluent.fr
Contact Person Name
Dorothée CHOCTEAU
Site Name
CHP Sainte Marie Osny
Department Name
Oncologie
Principal Investigator Name
Antoine BRUNA
Principal Investigator Email
a.bruna@crom95.com
Contact Person Name
Antoine BRUNA
Contact Person Email
a.bruna@crom95.com
Site Name
Oncoradio Centre Oncogard
Department Name
Oncologie
Principal Investigator Name
Eric LEGOUFFE
Principal Investigator Email
e.legouffe@oncogard.com
Contact Person Name
Eric LEGOUFFE
Contact Person Email
e.legouffe@oncogard.com
Site Name
Institut Gustave Roussy
Department Name
Oncologie
Principal Investigator Name
Benjamin Verret
Principal Investigator Email
benjamin.verret@gustaveroussy.fr
Contact Person Name
Benjamin Verret
Site Name
Clinique Pasteur Lanroze
Department Name
Oncologie
Principal Investigator Name
Matthieu CHASSERAY
Principal Investigator Email
m.chasseray@oncologie-brest.fr
Contact Person Name
Matthieu CHASSERAY
Contact Person Email
m.chasseray@oncologie-brest.fr
Site Name
Centre D'Oncologie Et De Radiotherapie 37
Department Name
Oncologie
Principal Investigator Name
Tévy SAN
Principal Investigator Email
t.san@cort37.fr
Contact Person Name
Tévy SAN
Contact Person Email
t.san@cort37.fr
Site Name
Institut De Cancerologie De L Ouest (Saint-Herblain Cedex)
Department Name
Oncologie
Principal Investigator Name
Marie ROBERT
Principal Investigator Email
marie.robert@ico.unicancer.fr
Contact Person Name
Marie ROBERT
Contact Person Email
marie.robert@ico.unicancer.fr
Site Name
Centre Leon Berard
Department Name
Oncologie
Principal Investigator Name
Benoite MERY
Principal Investigator Email
benoite.mery@lyon.unicancer.fr
Contact Person Name
Benoite MERY
Contact Person Email
benoite.mery@lyon.unicancer.fr
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Oncologie
Principal Investigator Name
Laurence VENAT
Principal Investigator Email
laurence.venat@chu-limoges.fr
Contact Person Name
Laurence VENAT
Contact Person Email
laurence.venat@chu-limoges.fr
Site Name
CARIO Centre Armoricain de Radiotherapie D'Imagerie medicale et D'Oncologie
Department Name
Oncologie
Principal Investigator Name
Anne-Claire HARDY BESSARD
Principal Investigator Email
ac.hardy@cario-sante.fr
Contact Person Name
Anne-Claire HARDY BESSARD
Contact Person Email
ac.hardy@cario-sante.fr
Site Name
Institut Curie (26 Rue D Ulm)
Department Name
Oncologie
Principal Investigator Name
Nicolas KIAVUE
Principal Investigator Email
nicolas.kiavue@curie.fr
Contact Person Name
Nicolas KIAVUE
Contact Person Email
nicolas.kiavue@curie.fr
Site Name
Centre Regional Lutte Contre Le Cancer (Strasbourg)
Department Name
Oncologie Médicale
Principal Investigator Name
Carole PFLUMIO
Principal Investigator Email
c.pflumio@icans.eu
Contact Person Name
Carole PFLUMIO
Contact Person Email
c.pflumio@icans.eu
Site Name
Centr Georges Francois Leclerc
Department Name
Oncologie Médicale
Principal Investigator Name
Isabelle DESMOULIN
Principal Investigator Email
IDesmoulins@cgfl.fr
Contact Person Name
Isabelle DESMOULIN
Contact Person Email
IDesmoulins@cgfl.fr
Site Name
Assistance Publique Hopitaux De Paris (20 Rue Leblanc)
Department Name
Oncologie Médicale
Principal Investigator Name
Jacques MEDIONI
Principal Investigator Email
Jacques.medioni@aphp.fr
Contact Person Name
Jacques MEDIONI
Contact Person Email
Jacques.medioni@aphp.fr
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Oncologie Médicale
Principal Investigator Name
Nicolas ISAMBERT
Principal Investigator Email
nicolas.isambert@chu-poitiers.fr
Contact Person Name
Nicolas ISAMBERT

Sponsor

Primary sponsor

Full Name
Unicancer
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
TRASTUZUMAB
Active Substance
TRASTUZUMAB
Modality
Monoclonal antibody
Routes Of Administration
SOLUTION FOR INFUSION / SOLUTION FOR INJECTION
Route
Solution for infusion/injection
Investigational Product Name
TRASTUZUMAB EMTANSINE
Active Substance
TRASTUZUMAB EMTANSINE
Modality
ADC
Routes Of Administration
SOLUTION FOR INFUSION
Route
Solution for infusion
Investigational Product Name
TRASTUZUMAB DERUXTECAN
Active Substance
TRASTUZUMAB DERUXTECAN
Modality
ADC
Routes Of Administration
SOLUTION FOR INJECTION
Route
Solution for injection
Investigational Product Name
PERTUZUMAB
Active Substance
PERTUZUMAB
Modality
Monoclonal antibody
Routes Of Administration
SOLUTION FOR INJECTION
Route
Solution for injection

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