A Study of Giredestrant in Participants With Grade 1 Endometrial Cancer (EndomERA)

A Phase II, Single-Arm Study of Giredestrant in Patients With Grade 1 Endometrial Cancer

This Phase II, global, single-arm study is designed to evaluate the efficacy, safety, and pharmacokinetics of giredestrant monotherapy in participants with Grade 1 endometrioid endometrial cancer.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: Giredestrant

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: CO44195 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Centre - Glen Site
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Recruiting
      • Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Recruiting
      • Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Poland
  • Gliwice, Poland, 44-101
    • Recruiting
    • Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.
  • Kielce, Poland, 25-734
    • Recruiting
    • Swietokrzyskie Centrum Onkologii; Klinika Ginekologii
  • Warszawa, Poland, 02-781
    • Recruiting
    • Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie;Klinika Ginekologii Onkologicznej
• United States
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Recruiting
      • Arizona Oncology - HOPE Wilmot
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Active, not recruiting
      • Mount Sinai Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Recruiting
      • Minnesota Oncology Minneapolis
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Recruiting
      • Nebraska Methodist Hospital
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Active, not recruiting
      • Englewood Health/Hematology Oncology Practice of Englewood (HOPE)
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Portland Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • Western Pennsylvania Hospital
  • Texas
    • Austin, Texas, United States, 78731
      • Recruiting
      • Texas Oncology Cancer Center
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Texas Oncology, P.A. - Fort Worth
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed Grade 1 endometrial cancer (EC) of endometrioid histology for which participants are willing to receive 6-cycles of study therapy. An endometrial biopsy (EMB) or dilation and curettage (D&C) fresh collected within the screening period or archival sample collected within 3 months prior to screening must be provided to a central laboratory for histologic confirmation to determine eligibility.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Magnetic resonance imaging (MRI)-confirmation of non-deeply invasive tumor (<50% myometrial invasion)
• MRI or computed tomography (CT)-confirmation of no extrauterine disease
• Willing to undergo a minimum of 6 continuous cycles of therapy before decision on surgery
• No prior treatment for endometrial cancer
• Able and willing to take oral medications
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Adequate hematologic and end-organ function, as defined in the protocol
• Negative HIV test at screening, with the following exception: Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥200/μL, and have an undetectable viral load.
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs, during the treatment period and for 30 days after the final dose of giredestrant, as defined in the protocol

Exclusion Criteria:

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 30 days after the final dose of giredestrant or within the time period specified per local prescribing guidelines after the final dose of the investigator's choice of endocrine therapy
• Participants with non-endometrioid histologies, such as serous, clear cell, and mixed
• Treatment with investigational therapy within 28 days prior to initiation of study enrollment
• Treatment for cancer including but not limited to, chemotherapy, immunotherapy, cyclin-dependent kinase (CDK)4/6 inhibitors, endocrine therapy, biologic therapy, or herbal therapy within 28 days prior to the initiation of study enrollment
• Any gastrointestinal condition causing malabsorption or obstruction (e.g., celiac sprue, gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind loop syndrome)
• Known hypersensitivity to giredestrant or its excipients
• Known intercurrent illness or psychiatric illness/social situations that will limit compliance with study requirements
• Evidence or high suspicion of metastatic/extrauterine disease at enrollment
• Unwilling or unable to comply with study-related procedures, including all endometrial sampling/biopsies
• Planned surgery, either for the treatment of cancer or any other surgery, during the study treatment period and up to 10 days after the completion of study treatment
• Serious infections requiring IV antibiotics within 7 days prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact participant safety
• Participants who have clinically significant liver disease consistent with Child-Pugh Class B or C, including active hepatitis (e.g., hepatitis B virus [HBV] or hepatitis C virus [HCV]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis, as defined in the protocol
• Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
• Any serious medical condition or abnormality in clinical laboratory tests that precludes the participant's safe participation in and completion of the study
• History of other malignancy within 5 years prior to screening, except for those with an expected negligible risk for metastases or death (e.g., 5-year overall survival 90%) after curative treatment
• Active tuberculosis
• Severe infection per investigator judgment at the time of enrollment, including but not limited to, use of systemic antibiotics, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact participant safety
• Significant cardiovascular disease, such as cardiac disease New York Heart Association Class II or greater, myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina
• Active cardiac disease or history of cardiac dysfunction, as defined in the protocol
• Major surgical procedure other than for diagnosis within 28 days prior to enrollment or anticipation of need for a major surgical procedure during the study
• Prior allogeneic bone marrow transplantation or solid organ transplant
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high risk for treatment complications illnesses or conditions that interfere with the participant's capacity to understand, follow, and/or comply with study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Giredestrant

Drug: Giredestrant; Participants will receive giredestrant 30 milligrams (mg) taken orally (PO) once a day (QD) on Days 1 to 28 of each 28-day cycle for 6 cycles. After completion of 6 cycles, the participant and investigator can choose to continue study treatment for an additional 18 cycles or discontinue study treatment and receive investigator-determined care.; Other Names: GDC-9545; RO7197597; RG6171

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with at Least One Adverse Event, with Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)		From Baseline until 30 days after the final dose of study drug (up to 1 year, 6 months)
Percentage of Participants Who Have Regression at 6 Months	The percentage of participants who have regression is defined as participants who have a decrease in the proportion of cancer in their endometrial biopsy or the proportion of cancer is not increased, but there is an increase in non-cancer/non-atypical hyperplasia at the 6-month assessment compared with baseline.	Baseline, 6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of Giredestrant at Specified Timepoints		Predose on Day 1 of Cycles 1, 2, 3, 4, and 6; 3-4 hours Postdose on Day 1 of Cycles 1 and 2 (each cycle is 28 days)
Percentage of Participants Who Have Complete Regression at 6 Months	The percentage of participants who have complete regression is defined as participants having an assessment of 100% of non-cancer/non-atypical hyperplasia at the Month 6 assessment.	Baseline, 6 Months
Median Duration of Regression		From first regression to first relapse (up to 1 year, 6 months)
Median Time to First Regression		From first study treatment to first regression (up to 1 year, 6 months)
Median Time to Relapse or Loss of Clinical Benefit		From first study treatment to relapse or loss of clinical benefit, whichever occurs first (up to 1 year, 6 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms
• Other Study ID Numbers: CO44195; 2022-002443-21 (EudraCT Number); 2023-504091-23-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No