Clinical trial • Phase III • Oncology

GIREDESTRANT for Breast cancer (estrogen receptor–positive, HER2-negative, locally advanced or metastatic)

Phase III trial of GIREDESTRANT for Breast cancer (estrogen receptor–positive, HER2-negative, locally advanced or metastatic).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Breast cancer (estrogen receptor–positive, HER2-negative, locally advanced or metastatic)
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
24-04-2024
First CTIS Authorization Date
06-06-2024

Trial design

Randomised, open-label, physician’s choice of endocrine therapy plus everolimus. comparator endocrine therapy options listed include fulvestrant (faslodex 250 mg solution for injection, intramuscular), tamoxifen (tamoxifen 20 mg tablets), exemestane (exemestane 25 mg tablets) and other licensed endocrine agents; everolimus (various formulations; typical max daily dose listed 10 mg oral) is administered in combination in the comparator arm. test arm: giredestrant (ro7197597) plus everolimus (everolimus 10 mg oral daily as indicated by product entries).-controlled Phase III trial in Germany, Greece, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Physician’s choice of endocrine therapy plus everolimus. Comparator endocrine therapy options listed include fulvestrant (Faslodex 250 mg solution for injection, intramuscular), tamoxifen (Tamoxifen 20 mg tablets), exemestane (Exemestane 25 mg tablets) and other licensed endocrine agents; everolimus (various formulations; typical max daily dose listed 10 mg oral) is administered in combination in the comparator arm. Test arm: giredestrant (RO7197597) plus everolimus (everolimus 10 mg oral daily as indicated by product entries).
Biomarker Stratified
True, ESR1 mutation (ESR1m) status — ESR1m subpopulation versus overall ITT population (ESR1m determined by central ctDNA testing prior to randomization)
Target Sample Size
308

Eligibility

Recruits 308 The study has vulnerable-population materials and specific consents: infant/newborn authorization forms, pregnant-partner ICFs and newborn-data ICFs are present in the document list (e.g. "L1_ML43171_ICF Infant Authorization Form_IT", "L1_ML43171_Pregnant-Partner-ICF_DE_German_Public", "L3_ML43171_Newborn_data_ICF_ES_Spanish_Public"). Patient-facing/child materials (e.g. "Understanding Cancer for Kids 7-12") are also included. Consent/assent handling uses specific information and ICF documents for these groups and separate optional/biobanking ICFs; materials are provided in multiple country/language versions (English, Greek, German, Italian, Spanish) as indicated by the translated ICF/document files..

Vulnerable Population
The study has vulnerable-population materials and specific consents: infant/newborn authorization forms, pregnant-partner ICFs and newborn-data ICFs are present in the document list (e.g. "L1_ML43171_ICF Infant Authorization Form_IT", "L1_ML43171_Pregnant-Partner-ICF_DE_German_Public", "L3_ML43171_Newborn_data_ICF_ES_Spanish_Public"). Patient-facing/child materials (e.g. "Understanding Cancer for Kids 7-12") are also included. Consent/assent handling uses specific information and ICF documents for these groups and separate optional/biobanking ICFs; materials are provided in multiple country/language versions (English, Greek, German, Italian, Spanish) as indicated by the translated ICF/document files.

Inclusion criteria

  • {"criterion_text":"- Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent"}
  • {"criterion_text":"- Documented estrogen receptor-positive (ER+) tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) or European Society for Medical Oncology (ESMO) guidelines, assessed locally and defined as >= 1% of tumor cells stained positive based on the most recent tumor biopsy (or archived tumor sample)"}
  • {"criterion_text":"- Documented human epidermal growth factor receptor 2 (HER2)-negative tumor assessed locally"}
  • {"criterion_text":"- Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA) ESR1 mutation status determination by central testing prior to study treatment randomization"}
  • {"criterion_text":"- Measurable disease as defined per RECIST v.1.1 or evaluable bone metastases which must have at least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed"}
  • {"criterion_text":"- Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade ≤ 1"}

Exclusion criteria

  • {"criterion_text":"- Prior treatment with another oral selective estrogen receptor degrader (SERD), proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), novel oral selective estrogen receptor modulator (SERM) or everolimus in any setting. Prior fulvestrant is allowed if treatment was terminated at least 28 days prior to randomization. Prior treatment with tamoxifen is allowed."}
  • {"criterion_text":"- Progression on more than 2 prior lines of systemic endocrine therapy in the locally advanced unresectable or metastatic breast cancer setting"}
  • {"criterion_text":"- Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 14 days or 5 drug elimination half-lives prior to randomization"}
  • {"criterion_text":"- History of any other malignancy other than breast cancer within 5 years prior to screening except for appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, papillary thyroid cancer treated with surgery, Stage I endometrial cancer or other non-breast cancers at very low risk of recurrence"}
  • {"criterion_text":"- Patients known to be positive for human immunodeficiency viruses (HIV) are excluded if they meet any of the following criteria: - CD4+ T-cell count of < 350 cells/µL - Detectable HIV viral load - History of an opportunistic infection within the past 12 months - On stable antiretroviral therapy for < 4 weeks"}
  • {"criterion_text":"- Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection, potentially affecting enteral absorption, or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. PFS in the ESR1m subpopulation determined by the investigator","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 2. PFS in the ITT population, determined by the investigator, PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)","definition_or_measurement_approach":"PFS defined as time from randomization to first occurrence of disease progression or death from any cause, determined by investigator per RECIST v1.1"}

Secondary endpoints

  • {"endpoint_text":"- 1. OS after randomization, defined as the time from randomization to death from any cause","definition_or_measurement_approach":"Time from randomization to death from any cause"}
  • {"endpoint_text":"- 2.ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to RECIST v1.1","definition_or_measurement_approach":"Proportion of patients with CR or PR on two consecutive occasions ≥4 weeks apart per investigator using RECIST v1.1"}
  • {"endpoint_text":"- 3.DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1","definition_or_measurement_approach":"Time from first documented objective response to progression or death per investigator using RECIST v1.1"}
  • {"endpoint_text":"- 4.CBR, defined as the proportion of patients with stable disease for >= 24 weeks or a CR or PR on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to RECIST v1.1","definition_or_measurement_approach":"Proportion with stable disease ≥24 weeks or CR/PR on two occasions ≥4 weeks apart per RECIST v1.1"}
  • {"endpoint_text":"- 5.TTCD in pain severity, defined as the time from randomization to the first documentation of a ≥2-point increase from baseline on the \"worst pain\" item score from the Brief Pain Inventory-Short Form (BPI-SF) held for two consecutive time points, or a ≥2-point increase followed by death attributable to cancer progression within 28 days from the last assessment","definition_or_measurement_approach":"Time from randomization to first documentation of ≥2-point increase from baseline on BPI-SF 'worst pain' item held for two consecutive timepoints or ≥2-point increase followed by cancer-related death within 28 days"}
  • {"endpoint_text":"- 6.TTCD in pain presence and interference after randomization, defined as the time from randomization to the first documentation of >= 10-point increase in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 Questionnaire (QLQ-C30) linearly transformed pain scale score held for two consecutive time points, or a >=10-point increase followed by death attributable to cancer progression within 28 days from the last assessment","definition_or_measurement_approach":"Time from randomization to first documentation of ≥10-point increase in EORTC QLQ-C30 pain scale held for two consecutive timepoints or ≥10-point increase followed by cancer-related death within 28 days"}
  • {"endpoint_text":"- 7.TTCD in PF after randomization, defined as the time from randomization to the first documentation of >= 10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed PF scale score held for two consecutive time points, or a >= 10-point decrease followed by death attributable to cancer progression within 28 days from the last assessment","definition_or_measurement_approach":"Time from randomization to first documentation of ≥10-point decrease from baseline in EORTC QLQ-C30 Physical Functioning score held for two consecutive timepoints or ≥10-point decrease followed by cancer-related death within 28 days"}
  • {"endpoint_text":"- 8.TTCD in RF after randomization, defined as the time from randomization to the first documentation of >= 10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed RF scale score held for two consecutive time points, or a >= 10-point decrease followed by death attributable to cancer progression within 28 days from the last assessment","definition_or_measurement_approach":"Time from randomization to first documentation of ≥10-point decrease from baseline in EORTC QLQ-C30 Role Functioning score held for two consecutive timepoints or ≥10-point decrease followed by cancer-related death within 28 days"}
  • {"endpoint_text":"- 9.TTCD in HRQoL after randomization, defined as the time from randomization to the first documentation of >= 10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed GHS/QoL scale score held for two consecutive time points, or a >= 10-point decrease followed by death attributable to cancer progression within 28 days from the last assessment","definition_or_measurement_approach":"Time from randomization to first documentation of ≥10-point decrease from baseline in EORTC QLQ-C30 global health status/QoL score held for two consecutive timepoints or ≥10-point decrease followed by cancer-related death within 28 days"}
  • {"endpoint_text":"- 10.Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0","definition_or_measurement_approach":"Incidence and severity graded per NCI CTCAE v5.0"}
  • {"endpoint_text":"- 11.Change from baseline in targeted vital signs","definition_or_measurement_approach":"Change from baseline in specified vital signs"}
  • {"endpoint_text":"- 12.Change from baseline in targeted clinical laboratory test results","definition_or_measurement_approach":"Change from baseline in specified clinical laboratory tests"}
  • {"endpoint_text":"- 13. Plasma concentration of giredestrant at specified timepoints","definition_or_measurement_approach":"Plasma PK sampling for giredestrant at specified timepoints"}

Recruitment

Planned Sample Size
308
Recruitment Window Months
32
Consent Approach
Informed consent is obtained using subject information and ICF documents provided in multiple languages (English, Greek, German, Italian, Spanish). Main ICFs and IAF/optional/biobanking forms are provided per country (e.g. 'L1_ML43171_Main ICF' in Greek/English/German/Spanish/Italian, 'L1_ML43171_Biobanking-ICF_DE', 'L1_ML43171_ICF Infant Authorization Form_IT', 'L2_ML43171_Pregnant_Partner_ICF_ES'). Vulnerable-subject-specific consent forms (infant authorization, newborn data ICF, pregnant-partner ICF) and optional consent modules are supplied; consent is therefore handled via standard ICFs with separate age- or role-specific forms where applicable and in country-appropriate languages.

Methods

  • Newspaper adverts (country-specific PDFs present: e.g. 'Newspaper AD' documents in Greek, German, Spanish) — channel: print/press; target: patients/public in respective country (Greece, Germany, Spain).
  • Posters and trifold leaflets (country-specific: e.g. 'Recruitment Poster', 'Trifold' files for GR/DE/ES/IT) — channel: site-based printed materials; target: patients at participating sites in each country.
  • HCP letters and GP letters (e.g. 'HCP_Letter_ES', 'GP-Letter_IT') — channel: direct letter to healthcare professionals/GPs; target: clinicians to inform about trial and recruitment.
  • Patient-facing materials and educational leaflets for children/families (e.g. 'Understanding Cancer for Kids 7-12', 'Understanding Your Condition and Study') — channel: site distribution; target: family members/children of participants.
  • Study welcome guides, study schedule planners, tote bags and coordinator tearpads (e.g. 'Study Welcome Guide_DE', 'Study Schedule Planner') — channel: on-site participant engagement materials; target: enrolled participants.
  • Country-specific recruitment arrangements documents (K1 documents present for Germany, Greece, Italy, Spain) describing local recruitment materials and approaches in those countries.

Geography

Total Number Of Sites
41
Total Number Of Participants
59

Germany

Earliest CTIS Part Ii Submission Date
15-05-2024
Latest Decision Or Authorization Date
05-12-2024
Processing Time Days
204
Number Of Sites
10
Number Of Participants
10

Sites

Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Contact Person Name
Marcus Schmidt
Site Name
St. Johannes Hospital
Contact Person Name
Darina Kodzhabasheva
Site Name
Franziskus Hospital Harderberg
Contact Person Name
Kerstin Lüdtke-Heckenkamp
Site Name
Dr. Apel Medizinische Versorgung GmbH
Contact Person Name
Klaus Apel
Contact Person Email
k.apel@praxis-apel.de
Site Name
Universitaetsklinikum des Saarlandes AöR
Department Name
Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin
Contact Person Name
Julia Radosa
Contact Person Email
julia.radosa@uks.eu
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Frauenklinik, Abteilung, Gynäkologische Onkologie
Contact Person Name
Peter A. Fasching
Site Name
Universitaetsklinikum Duesseldorf AöR
Contact Person Name
Eugen Ruckhäberle
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Brustzentrum
Contact Person Name
Joke Tio
Contact Person Email
joke.tio@ukmuenster.de
Site Name
Marienhospital Bottrop gGmbH
Contact Person Name
Hans-Christian Kolberg
Site Name
National Center For Tumor Diseases (NCT) Heidelberg
Department Name
Nationales Zentrum für Tumorerkrankungen (NCT)
Contact Person Name
Andreas Schneeweiss

Greece

Earliest CTIS Part Ii Submission Date
15-05-2024
Latest Decision Or Authorization Date
17-12-2024
Processing Time Days
216
Number Of Sites
12
Number Of Participants
12

Sites

Site Name
General University Hospital Of Larissa
Department Name
Oncology clinic
Contact Person Name
Athanasios Kotsakis
Contact Person Email
thankotsakis@hotmail.com
Site Name
St. Luke's Hospital S.A.
Department Name
Department of Medical Oncology
Contact Person Name
Georgios Fountzilas
Contact Person Email
fountzil@auth.gr
Site Name
University General Hospital Of Heraklion
Department Name
Internal Medicine – Oncology Clinic
Contact Person Name
Dimitrios Mavroudis
Contact Person Email
medoncsec@med.uoc.gr
Site Name
Metaxa Cancer Center Hospital Of Piraeus
Department Name
Medical Oncology
Contact Person Name
Christos Kosmas
Contact Person Email
ckosmas1@hotmail.com
Site Name
General University Hospital Of Patras
Department Name
Division of Oncology
Contact Person Name
Angelos Koutras
Contact Person Email
angkoutr@otenet.gr
Site Name
Athens Medical Center S.A.
Department Name
Oncology Clinic
Contact Person Name
Sofia Baka
Contact Person Email
bakasofia@hotmail.com
Site Name
University General Hospital Attikon
Department Name
2nd Propaedeutic Internal Medicine Department
Contact Person Name
Amanda Psyrri
Contact Person Email
Psyrri237@yahoo.com
Site Name
Alexandra Hospital
Department Name
Haematology-Oncology department of Therapeutic Clinic
Contact Person Name
Flora Zagouri
Contact Person Email
florazagouri@yahoo.co.uk
Site Name
Euromedica General Clinic Of Thessaloniki
Department Name
Oncology Department
Contact Person Name
Konstantinos Papazisis
Contact Person Email
k.papazisis@oncomedicare.com
Site Name
Metropolitan General Hospital Healthcare Facilities Operation And Management Single Member S.A.
Department Name
Oncology and Clinical trials and research Clinic
Contact Person Name
Panagiotis Katsaounis
Site Name
Olympion Therapeftirio General Clinic Of Patras S.A.
Department Name
Pathological Division of Oncology
Contact Person Name
Haralabos Kalofonos
Contact Person Email
ckalofonos@olympion-sa.gr
Site Name
Iaso Private General Obstetrics Gynecological & Pediatric Clinic Diagnostic Therapeutic & Research Center S.A.
Department Name
Obstetrics - Gynecology Clinic, B’ Oncology Clinic
Contact Person Name
Stylianos Giassas
Contact Person Email
sgiassas@yahoo.com

Italy

Earliest CTIS Part Ii Submission Date
15-05-2024
Latest Decision Or Authorization Date
17-12-2024
Processing Time Days
216
Number Of Sites
8
Number Of Participants
9

Sites

Site Name
Azienda Ospedaliera Universitaria Integrata Verona
Department Name
Dipartimento di Oncologia
Contact Person Name
Elena Fiorio
Contact Person Email
elena.fiorio@aovr.veneto.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
Oncologia Medica
Contact Person Name
Lucia Del Mastro
Contact Person Email
lucia.delmastro@hsanmartino.it
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
Dipartimento Ematologia, Oncologia e Medicina Molecolare (Oncologia Falck)
Contact Person Name
Emiliana Tarenzi
Site Name
Azienda Ospedaliero Universitaria Di Modena
Department Name
Medical Oncology
Contact Person Name
Luca Moscetti
Contact Person Email
moscetti.luca@aou.mo.it
Site Name
Universita' Degli Studi Di Ferrara
Department Name
Medical Oncology
Contact Person Name
Alessio Schirone
Contact Person Email
a.schirone@ospfe.it
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
Department of clinical and experimental oncology (UOSD Phase 4 Clinical Unit)
Contact Person Name
Patrizia Vici
Contact Person Email
patrizia.vici@ifo.it
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
Breast Unit (Phase 1 Research Center)
Contact Person Name
Marina Elena Cazzaniga
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Clinica di Oncologia Medica
Contact Person Name
Rossana Berardi

Spain

Earliest CTIS Part Ii Submission Date
15-05-2024
Latest Decision Or Authorization Date
12-05-2025
Processing Time Days
362
Number Of Sites
11
Number Of Participants
28

Sites

Site Name
Hospital Clinico Universitario De Valencia
Department Name
Servicio de Oncología
Contact Person Name
Begoña Bermejo de las Heras
Contact Person Email
begobermejo@gmail.com
Site Name
Hospital Universitari Dexeus Grupo Quironsalud
Department Name
Servicio de Oncología
Contact Person Name
Javier Cortés Castán
Contact Person Email
javier.cortes@maj3.health
Site Name
Hospital Clinico San Carlos
Department Name
Servicio de Oncología
Contact Person Name
José Ángel García Sáenz
Contact Person Email
jagsaenz@yahoo.com
Site Name
Hospital Clinic De Barcelona
Department Name
Servicio de Oncología
Contact Person Name
Francesco Schettini
Contact Person Email
SCHETTINI@recerca.clinic.cat
Site Name
Hospital Universitario 12 De Octubre
Department Name
Servicio de Oncología
Contact Person Name
Pablo Tolosa Ortega
Contact Person Email
pablotolosa_7@hotmail.com
Site Name
Hospital Universitario Virgen De Las Nieves
Department Name
Servicio de Oncología
Contact Person Name
Encarnación González Flores
Site Name
Hospital Universitario Reina Sofia
Department Name
Servicio de Oncología
Contact Person Name
Juan de la Haba Rodríguez
Contact Person Email
juahaba@gmail.com
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Servicio de Oncología
Contact Person Name
Yolanda Jerez Gilarranz
Contact Person Email
itacayoli@hotmail.com
Site Name
Hospital General Universitario Morales Meseguer
Department Name
Servicio de Oncología
Contact Person Name
Esmeralda García Torralba
Contact Person Email
esmeralda.garciat@um.es
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Servicio de Oncología
Contact Person Name
Silvia Antolín Novoa
Contact Person Email
silvia.antolin.novoa@sergas.es
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Servicio de Oncología
Contact Person Name
Elena López Miranda
Contact Person Email
elemiranda@hotmail.com

Sponsor

Primary sponsor

Full Name
Genentech Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Pharmaceutical Product Development LLC
Responsibilities
Global CRO
Name
PPD Global Ltd.
Responsibilities
sponsorDuties code: 1

Third parties

  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"EDC provider","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"sponsorDuties code: 6","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Kayentis","duties_or_roles":"Patient Recruitment","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Global CRO","organisation_type":"Pharmaceutical company"}
  • {"country":"Greece","full_name":"PPD Global Ltd.","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
RO7197597
Active Substance
GIREDESTRANT
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Not authorised (prodAuthStatus 1)
Maximum Dose
30 mg
Investigational Product Name
Everolimus (multiple marketed presentations listed, e.g. Afinitor, Everolimus Zentiva)
Active Substance
EVEROLIMUS
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (prodAuthStatus 2 for marketed presentations)
Frequency
Daily (max daily dose amount listed 10 mg)
Maximum Dose
10 mg
Combination Treatment
Yes

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