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

• ClinicalTrials.gov Identifier: NCT05634499
• Recruitment Status: Recruiting
• First Posted: December 2, 2022
• Last Update Posted: September 13, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Endometrial Cancer	Drug: Giredestrant	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Single-Arm Study of Giredestrant in Patients With Grade 1 Endometrial Cancer
• Actual Study Start Date: June 27, 2023
• Estimated Primary Completion Date: October 30, 2024
• Estimated Study Completion Date: October 30, 2024

Arms and Interventions

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 therapy or discontinue study therapy and receive investigator-determined care. After 6 months, participants can discontinue study treatment and undergo surgery or continue to receive study treatment for up to 18 additional cycles, per shared decision-making by the participant and physician.; Other Names: RO7197597; GDC-9545; RG6171

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Who Have Regression at 6 Months [ Time Frame: Baseline, 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 have an increase in non-cancer/non-atypical hyperplasia at the 6-month assessment compared with baseline.
2. 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) [ Time Frame: From Baseline until 30 days after the final dose of study drug (up to 1 year, 6 months) ]

Secondary Outcome Measures :

1. Percentage of Participants Who Have Complete Regression at 6 Months [ Time Frame: Baseline, 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.
2. Median Duration of Regression [ Time Frame: From first regression to first relapse (up to 1 year, 6 months) ]
3. Median Time to First Regression [ Time Frame: From first study treatment to first regression (up to 1 year, 6 months) ]
4. Median Time to Relapse or Loss of Clinical Benefit [ Time Frame: From first study treatment to relapse or loss of clinical benefit, whichever occurs first (up to 1 year, 6 months) ]
5. Plasma Concentration of Giredestrant at Specified Timepoints [ Time Frame: 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) ]

Eligibility Criteria

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

Criteria

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 2 months prior to screening must be provided to a central laboratory for histologic confirmation to determine eligibility.
• Life expectancy ≥12 weeks
• 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
• 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)
• Has been on any hormonal treatment (including progestin-containing intrauterine device [IUD]) for complex atypical hyperplasia (CAH)/EIN or Grade 1 EC in the last 3 months
• Use hormone replacement therapy (including systemic or topical estrogen, progesterone, or testosterone based medication) or/and phytoestrogen supplements (i.e., black cohosh) or has been on progestin (including progestin-containing IUD), tamoxifen or aromatase inhibitor within the prior 3 months
• 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
• Substance abuse within 12 months prior to screening
• 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

Contacts and Locations

Contacts

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

Locations

United States, Arizona

Arizona Oncology - HOPE Wilmot; Recruiting

Tucson, Arizona, United States, 85710

United States, Florida

Mount Sinai Medical Center; Recruiting

Miami Beach, Florida, United States, 33140

United States, Minnesota

Minnesota Oncology Minneapolis; Recruiting

Minneapolis, Minnesota, United States, 55404

United States, New Jersey

Englewood Health/Hematology Oncology Practice of Englewood (HOPE); Recruiting

Englewood, New Jersey, United States, 07631

United States, Oregon

Providence Portland Medical Center; Recruiting

Portland, Oregon, United States, 97213

United States, Texas

Texas Oncology Cancer Center; Recruiting

Austin, Texas, United States, 78731

Texas Oncology, P.A. - Fort Worth; Recruiting

Fort Worth, Texas, United States, 76104

United States, Virginia

Virginia Oncology Associates; Recruiting

Norfolk, Virginia, United States, 23502

Canada, Quebec

Jewish General Hospital; Recruiting

Montreal, Quebec, Canada, H3T 1E2

McGill University Health Centre - Glen Site; Recruiting

Montreal, Quebec, Canada, H4A 3J1

Italy

Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica; Recruiting

Napoli, Campania, Italy, 80131

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS; Active, not recruiting

Meldola, Emilia-Romagna, Italy, 47014

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Recruiting

Roma, Lazio, Italy, 00168

Poland

Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.; Recruiting

Gliwice, Poland, 44-101

Swietokrzyskie Centrum Onkologii; Klinika Ginekologii; Recruiting

Kielce, Poland, 25-734

Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie;Klinika Ginekologii Onkologicznej; Recruiting

Warszawa, Poland, 02-781

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT05634499
• Other Study ID Numbers: CO44195; 2022-002443-21 ( EudraCT Number ); 2023-504091-23-00 ( Other Identifier: EU Trial Number )
• First Posted: December 2, 2022
• Last Update Posted: September 13, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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/).

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Endometrial Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases