ACTIVE_NOT_RECRUITING

A Study to Evaluate the Efficacy and Safety of Giredestrant in Combination With Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf) Versus Phesgo in Participants With Locally Advanced or Metastatic Breast Cancer (heredERA Breast Cancer)

Conditions

Locally Advanced or Metastatic Breast Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2022-07-18

Study Completion:2030-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05296798

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 * 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 * 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

Inclusion Criteria

Exclusion 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
* 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
* 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

Contacts and Locations

Principal Investigator

Clinical Trials

STUDY_DIRECTOR

Hoffmann-La Roche

Study Locations (Sites)

Arizona Clinical Research Center, Inc

Tucson, Arizona, 85715

United States

Los Angeles Hematology Oncology Medical Group

Los Angeles, California, 90017

United States

Cancer Specialists of North Florida

Jacksonville, Florida, 32256

United States

Carle Cancer Center

Urbana, Illinois, 61801

United States

Maryland Oncology Hematology - Annapolis

Annapolis, Maryland, 21401

United States

St. Joseph Mercy Hospital

Ann Arbor, Michigan, 48106

United States

Henry Ford Hospital

Detroit, Michigan, 48202

United States

St. Joseph Mercy Oakland

Pontiac, Michigan, 48341

United States

Queens Hospital Cancer Center

Jamaica, New York, 11432

United States

Clinical Research Alliance

Westbury, New York, 11590

United States

West Cancer Center

Germantown, Tennessee, 38138

United States

CHRISTUS Spohn Cancer Center - Shoreline

Corpus Christi, Texas, 78404

United States

Texas Oncology - DFW

Dallas, Texas, 75246

United States

Texas Oncology - El Paso

El Paso, Texas, 79902

United States

CHRISTUS St. Michael Health System

Texarkana, Texas, 75503

United States

Swedish Cancer Institute - Edmonds Campus

Edmonds, Washington, 98026

United States

Swedish Cancer Institute - Issaquah

Issaquah, Washington, 98029

United States

Swedish Cancer Institute

Seattle, Washington, 98104

United States

Collaborators and Investigators

Sponsor: Hoffmann-La Roche

Clinical Trials, STUDY_DIRECTOR, Hoffmann-La Roche

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-18

Study Completion Date2030-12-31

Study Record Updates

Study Start Date2022-07-18

Study Completion Date2030-12-31

Terms related to this study

Additional Relevant MeSH Terms

Locally Advanced or Metastatic Breast Cancer