A Study of Giredestrant in Patients with Grade 1 Endometrial Cancer

Start 14 Mar 2023 · Status Ongoing, recruitment ended · 2 EU/EEA countries · 6 sites · Protocol CO44195

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Ongoing, recruitment ended

Participants planned 46

Countries 2

Sites 6

Grade 1 Endometrial Cancer

To evaluate the efficacy of giredestrant by regression rate at the Month 6 assessment and to evaluate the safety and tolerability of giredestrant

Key facts

Sponsor: F. Hoffmann-La Roche AG
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Neoplasms [C04]
Trial duration: 14 Mar 2023 → ongoing
Decision date (initial): 2024-05-20
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes
Funding sources: F. Hoffmann-La Roche AG

External identifiers

EU CT number: 2023-504091-23-00
EudraCT number: 2022-002443-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To evaluate the efficacy of giredestrant by regression rate at the Month 6 assessment and to evaluate the safety and tolerability of giredestrant

Secondary objectives 5

To evaluate the efficacy of giredestrant by complete regression rate at the Month 6 assessment
To evaluate the efficacy of giredestrant by duration of regression
To evaluate the efficacy of giredestrant by time to regression
To evaluate the efficacy of giredestrant by time to relapse or loss of clinical benefit
To characterize the giredestrant pharmacokinetic (PK) profile

Conditions and MedDRA coding

Grade 1 Endometrial Cancer

Version	Level	Code	Term	System organ class
21.0	PT	10014733	Endometrial cancer	100000004864
21.0	PT	10014738	Endometrial cancer stage I	100000004864

Study design 1 period

#	Title	Allocation	Blinding	Roles blinded	Arms
1	Overall Design This is a Phase II, single-arm study is designed to evaluate the efficacy, safety, and pharmacokinetics of giredestrant monotherapy in participants with Grade 1 endometrioid EC.	Not Applicable	None

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Confirmed Grade 1 endometrial carcinoma (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
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
Adequate hematologic and end-organ function

Exclusion criteria 6

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
Treatment for cancer including but not limited to, chemotherapy, immunotherapy, cyclin-dependent kinase (CDK)4/6i, endocrine therapy, biologic therapy, or herbal therapy within 28 days prior to the initiation of study enrollment
Any gastrointestinal condition causing malabsorption or obstruction
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
Participants who have clinically significant liver disease consistent with Child-Pugh Class B or C, including active hepatitis, current alcohol abuse, cirrhosis, or positive test for viral hepatitis
Any serious medical condition or abnormality in clinical laboratory tests that precludes the participant’s safe participation in and completion of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Regression rate at Month 6 assessment, defined as participants who have a decrease in the proportion of cancer or percentage of cancer is not increased but have an increase in non-cancer/non-atypical hyperplasia (%) at the Month 6 assessment compared with baseline
2. Occurrence and severity of adverse events with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

Secondary endpoints 5

1. Complete regression rate, defined as the participants who have an assessment of 100% of non-cancer/non-atypical hyperplasia at Month 6 assessment
2. Duration of regression, defined as the time from the first regression to time of the first relapse
3. Time to regression, defined as the time from the first study treatment to the first regression
4. Time to relapse or loss of clinical benefit per investigator, defined as the time from the first study treatment to relapse or loss of clinical benefit per investigator, whichever occurs first. Participants will be censored if they have surgery at Month 6 and no relapse or loss of clinical benefit occurs before surgery
5. Plasma concentration of giredestrant at specified timepoints

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

RO7197597

PRD9491575 · Product

Active substance: Giredestrant
Substance synonyms: 3-((1R,3R)-1-(2,6-DIFLUORO-4-((1-(3-FLUOROPROPYL)AZETIDIN-3-YL)AMINO)PHENYL)-3-METHYL-1,3,4,9-TETRAHYDRO-2H-PYRIDO(3,4-B)INDOL-2-YL)-2,2-DIFLUOROPROPAN-1-OL, RG-6171, GDC-9545, RO7197597
Other product name: GDC-9545, Giredestrant
Pharmaceutical form: CAPSULE, HARD
Route of administration: ORAL
Max daily dose: 30 mg milligram(s)
Max total dose: 20.16 g gram(s)
Max treatment duration: 672 Day(s)
Authorisation status: Not Authorised
MA holder: F. HOFFMANN-LA ROCHE LTD
Paediatric formulation: No
Orphan designation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation: F. Hoffmann-La Roche AG
Address: Grenzacherstrasse 124
City: Basel
Postcode: 4058
Country: Switzerland

Scientific contact point

Organisation: F. Hoffmann-La Roche AG
Contact name: Trial Information System - TISL

Public contact point

Organisation: F. Hoffmann-La Roche AG
Contact name: Trial Information System - TISL

Third parties 8

Organisation	City, country	Duties
Almac Clinical Technologies LLC ORG-100043036	Souderton, United States	Other
CellCarta ORG-100039881	Antwerp, Belgium	Other
Labcorp Central Laboratory Services LP ORG-100032236	Indianapolis, United States	Other
Labcorp Central Laboratory Services SARL ORG-100011524	Meyrin, Switzerland	Other
Labcorp Early Development Laboratories Inc. ORG-100012865	Madison, United States	Other
IQVIA Limited ORG-100008655	Reading, United Kingdom	Other
Parexel International (IRL) Limited ORG-100022780	Dublin 2, Ireland	Data management
Cellcarta Naperville LLC ORG-100042145	Naperville, United States	Other

Locations

2 EU/EEA countries · 6 investigational sites

By country

Country	MS status	Planned subjects	Sites
Italy	Ongoing, recruitment ended	3	3
Poland	Ongoing, recruitment ended	6	3
Rest of world Korea, Republic of, Canada, Australia, United States, New Zealand	—	37	—

Investigational sites

Italy

3 sites · Ongoing, recruitment ended

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Unità Operativa Oncologia Medica Uro-Ginecologica, Via Mariano Semmola 52, 80131, Naples

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

UOC Ginecologia oncologica, Largo Francesco Vito 1, 00168, Rome

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

GDP Uro-Ginecologico, Via Piero Maroncelli 40, 47014, Meldola

Poland

3 sites · Ongoing, recruitment ended

Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Kielcach

Klinika Ginekologii im. prof. hab. dr n. med. Józefa Starzewskiego, Ul. Prezydenta Stefana Artwinskiego 3, 25-734, Kielce

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Klinika Ginekologii Onkologicznej, Ul. Wilhelma Konrada Roentgena 5, 02-781, Warsaw