Clinical Trials/NCT05296798

NCT05296798

Active, Not Recruiting

Phase 3

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

Hoffmann-La Roche213 sites in 9 countries922 target enrollmentJuly 18, 2022

ConditionsLocally Advanced or Metastatic Breast Cancer

InterventionsLHRH Agonist Optional Endocrine Therapy of Investigator's Choice Giredestrant Phesgo Docetaxel Paclitaxel

DrugsPhesgo Giredestrant Docetaxel Paclitaxel LHRH Agonist Optional Endocrine Therapy of Investigator's Choice

Overview

Phase: Phase 3
Intervention: LHRH Agonist
Conditions: Locally Advanced or Metastatic Breast Cancer
Sponsor: Hoffmann-La Roche
Enrollment: 922
Locations: 213
Primary Endpoint: Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1
Status: Active, Not Recruiting
Last Updated: 16 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

July 18, 2022

End Date

December 31, 2030

Last Updated

16 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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 to a maximum of eight cycles of induction therapy; the minimum cycles are defined as either: Phesgo injections + 4 docetaxel infusions, or Phesgo injections + 12 paclitaxel infusions

Exclusion Criteria

•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/m
•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).

Arms & Interventions

Arm A, Maintenance Therapy: Phesgo

Intervention: LHRH Agonist

Arm A, Maintenance Therapy: Phesgo

Intervention: Optional Endocrine Therapy of Investigator's Choice

Arm B, Maintenance Therapy: Giredestrant plus Phesgo

Intervention: LHRH Agonist

Arm B, Maintenance Therapy: Giredestrant plus Phesgo

Intervention: Giredestrant

Induction Therapy: Phesgo plus Taxane-Based Chemotherapy

Intervention: Phesgo

Arm B, Maintenance Therapy: Giredestrant plus Phesgo

Intervention: Phesgo

Induction Therapy: Phesgo plus Taxane-Based Chemotherapy

Intervention: Docetaxel

Arm A, Maintenance Therapy: Phesgo

Intervention: Phesgo

Induction Therapy: Phesgo plus Taxane-Based Chemotherapy

Intervention: Paclitaxel

Outcomes

Primary Outcomes

Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1

Time Frame: From randomization for maintenance therapy to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 53 months)

Secondary Outcomes

Overall Survival(From randomization for maintenance therapy to death from any cause (up to 98 months))
Objective Response Rate, as Determined by the Investigator According to RECIST v1.1(From randomization for maintenance therapy to disease progression or death (up to 53 months))
Duration of Response, as Determined by the Investigator According to RECIST v1.1(From first occurrence of documented objective response after randomization for maintenance therapy to disease progression or death from any cause, whichever occurs first (up to 53 months))
Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1(From randomization for maintenance therapy to disease progression or death (up to 53 months))
Mean Role Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire(Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years))
Mean Change from Baseline in the Role Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire(Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years))
Mean Physical Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire(Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years))
Mean Change from Baseline in the Physical Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire(Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years))
Mean Global Health Status/Quality of Life Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire(Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years))
Mean Change from Baseline in the Global Health Status/Quality of Life Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire(Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years))
Number of Participants with at Least One Adverse Event, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0)(From Baseline until 28 days after the final dose of study treatment (up to 8 years, 5 months))
Number of Participants with Abnormalities in Clinical Laboratory Test Results(From Baseline until 28 days after the final dose of study treatment (up to 8 years, 5 months))