Une étude de phase 3 pour évaluer l'efficacité et l'innocuité de Giredestrant en association avec Phesgo (pertuzumab, trastuzumab et hyaluronidase-zzxf) par rapport à Phesgo chez des patients atteints d'un cancer du sein localement avancé ou métastatique

Essai clinique

Type : Industriel
Statut : Ouvert
Phase : III
Étape du traitement : Traitements combinés
Date d'ouverture : 04/07/2022
Date clôture : 30/09/2032
Promoteur : Hoffmann-La Roche
Progression du cancer: Loco-régional et à distance
Résumé :

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.

Domaines/spécialités :
  • Cancer du sein
Biomarqueurs :
  • HER2
  • ER
Pathologies :
  • Tumeur maligne du sein - Cim10 : C50
Liens externes :

Critères de population

Sexe : Homme et femme
Age minimum : 18 ans
Critères d’inclusion :
  • 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
Critères d’exclusion :
  • 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 trastuzumab, with or without pertuzumab, or ado-trastuzumab emtansine in the adjuvant setting
  • 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
  • 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

Centre d'investigation

En cours
Nom : CHU de Besançon
Ville : BESANÇON (25)
RESPONSABLE MÉDICAL
Aucun responsable médical renseigné
CONTACT TECHNIQUE
Nom : BERTHOD
Prénom : Diane
Téléphone : 03 70 63 24 03
Email : dberthod@chu-besancon.fr

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