Informations générales (source: ClinicalTrials.gov)
A Phase III, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Giredestrant in Combination With Phesgo Versus Phesgo After Induction Therapy With Phesgo + Taxane in Patients With Previously Untreated HER2-Positive, Estrogen Receptor-Positive Locally-Advanced or Metastatic Breast Cancer
Interventional
Phase 3
Hoffmann-La Roche (Voir sur ClinicalTrials)
juillet 2022
septembre 2032
17 octobre 2024
This Phase III, randomized, two-arm, open-label, multicenter study will evaluate the
efficacy and safety of giredestrant plus Phesgo compared with Phesgo after induction
therapy with Phesgo plus taxane in participants with human epidermal growth factor
receptor 2 (HER2)-positive, estrogen receptor (ER)-positive advanced breast cancer
(metastatic or locally advanced disease not amenable to curative treatment) who have not
previously received a systemic non-hormonal anti-cancer therapy in the advanced setting.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:41 | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Catalan D' Oncologie - 66000 - Perpignan - France | Contact (sur clinicalTrials) | ||||
| CH de la Côte Basque - Hôpital de Bayonne - 64109 - Bayonne - France | Contact (sur clinicalTrials) | ||||
| CHD Vendée - 85025 - La Roche Sur Yon - France | Contact (sur clinicalTrials) | ||||
| CHU Besançon - Hôpital Jean Minjoz - 25030 - Besançon Cedex - France | Contact (sur clinicalTrials) | ||||
| CHU de GRENOBLE - 38043 - Grenoble - France | Contact (sur clinicalTrials) | ||||
| Hopital Prive Jean Mermoz - 69008 - Lyon - France | Contact (sur clinicalTrials) | ||||
| INSTITUT CURIE_Site Paris - 75005 - Paris - France | Contact (sur clinicalTrials) | ||||
| Institut Sainte Catherine;Recherche Clinique - 84918 - Avignon - France | Contact (sur clinicalTrials) | ||||
| Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie - 33077 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Histologically or cytologically confirmed and documented human epidermal growth
factor receptor 2 (HER2)-positive/estrogen receptor (ER)-positive adenocarcinoma of
the breast with metastatic or locally-advanced disease not amenable to curative
resection
- At least one measurable lesion and/or non-measurable disease evaluable according to
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Disease-free interval from completion of adjuvant or neoadjuvant systemic
non-hormonal treatment to recurrence of ≥6 months
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Left ventricular ejection fraction (LVEF) of at least (≥)50% measured by
echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
- Adequate hematologic and end-organ function
- For women of childbearing potential: Participants who agree to remain abstinent
(refrain from heterosexual intercourse) or use contraception, and agree to refrain
from donating eggs, during the treatment period and for 7 months after the final
dose of Phesgo
- For men: participants who agree to remain abstinent (refrain from heterosexual
intercourse) or use a condom, and agree to refrain from donating sperm, during the
treatment period and for 7 months after the final dose of Phesgo to avoid exposing
the embryo
Maintenance Phase Inclusion Criteria
- Complete a minimum of four cycles of induction therapy
- Achieve a minimum of stable disease (SD) (or Non-complete response
[CR]/Non-progressive disease [PD] for participants with non-measurable disease)
(i.e., did not experience PD) according to RECIST v1.1 at the last tumor assessment
during the induction therapy phase
- LVEF of ≥50% at the last assessment during the induction therapy phase
- Histologically or cytologically confirmed and documented human epidermal growth
factor receptor 2 (HER2)-positive/estrogen receptor (ER)-positive adenocarcinoma of
the breast with metastatic or locally-advanced disease not amenable to curative
resection
- At least one measurable lesion and/or non-measurable disease evaluable according to
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Disease-free interval from completion of adjuvant or neoadjuvant systemic
non-hormonal treatment to recurrence of ≥6 months
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Left ventricular ejection fraction (LVEF) of at least (≥)50% measured by
echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
- Adequate hematologic and end-organ function
- For women of childbearing potential: Participants who agree to remain abstinent
(refrain from heterosexual intercourse) or use contraception, and agree to refrain
from donating eggs, during the treatment period and for 7 months after the final
dose of Phesgo
- For men: participants who agree to remain abstinent (refrain from heterosexual
intercourse) or use a condom, and agree to refrain from donating sperm, during the
treatment period and for 7 months after the final dose of Phesgo to avoid exposing
the embryo
Maintenance Phase Inclusion Criteria
- Complete a minimum of four cycles of induction therapy
- Achieve a minimum of stable disease (SD) (or Non-complete response
[CR]/Non-progressive disease [PD] for participants with non-measurable disease)
(i.e., did not experience PD) according to RECIST v1.1 at the last tumor assessment
during the induction therapy phase
- LVEF of ≥50% at the last assessment during the induction therapy phase
- Previous systemic non-hormonal anti-cancer therapy in the metastatic breast cancer
(MBC) or advanced breast cancer (ABC) setting. Note: Up to one line of single-agent
endocrine therapy given in the metastatic or locally advanced setting will be
allowed.
- Prior treatment with a selective estrogen receptor degrader (SERD)
- Previous treatment with approved or investigative anti-HER2 agents in any breast
cancer treatment setting, except Phesgo (or trastuzumab SC with pertuzumab IV, or
pertuzumab and trastuzumab IV), single-agent trastuzumab IV or SC, ado-trastuzumab
emtansine, lapatinib, and neratinib in the neoadjuvant or adjuvant setting
- Disease progression within 6 months of receiving adjuvant anti-HER2 therapy (such as
trastuzumab, with or without pertuzumab [IV, SC, or fixed-dose combination], or
ado-trastuzumab emtansine, or neratinib)
- Non-resolution of all acute toxic effects of prior anti-cancer therapy or surgical
procedures to National Cancer Institute Common Terminology Criteria for Adverse
Events version 5.0 (NCI CTCAE v5.0) Grade 1 or better
- History of persistent Grade ≥2 (NCI-CTC, Version 5.0) hematological toxicity
resulting from previous adjuvant or neo-adjuvant therapy
- History of exposure to the following cumulative doses of anthracyclines; Doxorubicin
>360 mg/m2; Liposomal doxorubicin >500 mg/m2; Epirubucin >720 mg/m2; Mitoxantrone
>120 mg/m2; Idarubicin >90 mg/m2.
- Known active uncontrolled or symptomatic central nervous system (CNS) metastases,
carcinomatous meningitis, or leptomeningeal disease
- Dyspnea at rest due to complications of advanced malignancy, or other disease
requiring continuous oxygen therapy
- Pregnant or breastfeeding, or intending to become pregnant during the study or
within 7 months after the final dose of Phesgo (Women of childbearing potential must
have a negative serum pregnancy test result within 14 days prior to initiation of
induction therapy).
- Treated with investigational therapy within 28 days prior to initiation of induction
therapy
- Treated with localized palliative radiotherapy within 14 days prior to initiation of
induction therapy
- Concurrent participation in any other therapeutic clinical trial
- Known hypersensitivity to any of the study medications or to excipients of
recombinant human or humanized antibodies
- Current chronic daily treatment (continuous for >3 months) with corticosteroids
(dose of 10 mg/day methylprednisolone or equivalent)
- Poorly controlled hypertension
- Known clinically significant history of liver disease consistent with Child-Pugh
Class B or C, active liver disease including active viral or other hepatitis virus,
autoimmune hepatic disorders, or sclerosing cholangitis, current alcohol abuse, or
cirrhosis
- Active cardiac disease or history of cardiac dysfunction
- Major surgical procedure or significant traumatic injury within 14 days prior to
enrollment or anticipation of need for major surgery during induction therapy
- Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major
upper gastrointestinal surgery
- Concurrent, serious, uncontrolled infections, or known infection with HIV with the
following exception: Individuals who are HIV positive are eligible provided they are
stable on anti-retroviral therapy for ≥4 weeks, have a CD4 count ≥350 cells/uL, and
have an undetectable viral load and no history of AIDS-defining opportunistic
infections within 12 months prior to enrollment.
- Serious COVID-19 infection within 14 days prior to enrollment; however, no screening
testing for SARS-CoV-2 is required
- Serious infection requiring oral or IV antibiotics within 7 days prior to screening
- Any serious medical condition or abnormality in clinical laboratory tests that
precludes an individual's safe participation in the study
- History of malignancy within 5 years prior to screening with the exception of the
cancer under investigation in this study and malignancies with a negligible risk of
metastasis or death
- For pre- and perimenopausal women, and men: Known hypersensitivity to luteinizing
hormone-releasing hormone agonist (LHRHa); Not willing to undergo and maintain
treatment with approved LHRHa therapy for the duration of endocrine therapy that
requires gonadal function suppression
- Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5
drug-elimination half-lives, whichever is longer, prior to initiation of
giredestrant treatment in Arm B
- A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism,
including deep vein thrombosis, unless the condition is adequately treated and under
control