A Study of Giredestrant (GDC-9545) in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer

NCT03916744 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GO409872018-003798-85
• Study Type: interventional
• Target: 75
• Locations: 5 countries
• Sites: 15

Brief Summary

This study will evaluate the pharmacodynamics, pharmacokinetics, safety, and biologic activity of giredestrant in participants with Stage I-III operable estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, untreated breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Tumor Cell Proliferation, as Measured by the Proportion of Nuclei Staining Ki67-Positive at Surgery Relative to Baseline in Pre- and Post-Treatment Tumor Biopsy Samples

  The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the proportion of nuclei staining Ki67-positive (Ki67+) in the tumor biopsy sample taken post-treatment (at surgery) relative to that in the pre-treatment sample (at baseline).

  Baseline and Surgery (Day 15)

• Change From Baseline in Tumor Cell Proliferation, as Measured by the Difference in the Percentage of Nuclei Staining Ki67-Positive at Surgery Compared With Baseline in Pre- and Post-Treatment Tumor Biopsy Samples

  The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the percentage of nuclei staining Ki67-positive (Ki67+) in the pre- and post-treatment tumor biopsy samples (taken at baseline and surgery, respectively) and the absolute difference in the percentage of Ki67+ nuclei between the two samples (calculated as surgery minus baseline).

  Baseline and Surgery (Day 15)

Secondary Outcomes (10)

• Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0)

  From Baseline to Day 43

• Percentage of Participants With Abnormal Vital Signs During Treatment

  Baseline, Days 1, 8, and 15

• Change From Baseline in Pulse Rate

  Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)

• Change From Baseline in Systolic Blood Pressure

  Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)

• Change From Baseline in Diastolic Blood Pressure

  Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)

Study Arms (3)

Giredestrant 10 mg

EXPERIMENTAL

Drug: Giredestrant; Procedure: Surgery

Giredestrant 30 mg

EXPERIMENTAL

Drug: Giredestrant; Procedure: Surgery

Giredestrant 100 mg

EXPERIMENTAL

Drug: Giredestrant; Procedure: Surgery

Interventions

Giredestrant DRUG

Giredestrant will be administered orally once daily (QD) starting on Day 1 up to and including the day of surgery (if allowed per local process) on Day 15 (+/-2 days).

Also known as: GDC-9545, RO7197597, RG6171

Giredestrant 10 mg; Giredestrant 100 mg; Giredestrant 30 mg

Surgery PROCEDURE

Breast cancer surgery will take place on Day 15 (+/-2 days).

Giredestrant 10 mg; Giredestrant 100 mg; Giredestrant 30 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to comply with the study protocol, in the investigator's judgment
• Histologically confirmed invasive breast carcinoma, with all of the following characteristics: Primary tumor greater than or equal to (≥)1.5 centimeters (cm) in largest diameter by ultrasound; Stage I-III operable breast cancer; Documentation confirming the absence of distant metastasis (M0) as determined by institutional practice.
• ER-positive tumor and HER2-negative breast cancer as per local laboratory testing
• Postmenopausal status
• Breast cancer eligible for primary surgery
• Submission of a representative tumor tissue specimen
• Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (≤)1
• Adequate organ function

You may not qualify if:

• Diagnosis of inflammatory breast cancer
• Diagnosis of bilateral breast cancer
• Concurrent use of hormone replacement therapies
• Previous systemic or local treatment for the primary breast cancer currently under investigation
• Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry
• Current treatment with any systemic anti-cancer therapies
• Major surgery within 4 weeks prior to enrollment
• Radiation therapy within 2 weeks prior to enrollment
• Diagnosis of any secondary malignancy within 3 years prior to enrollment, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
• Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper gastrointestinal surgery including gastric resection
• Known HIV infection
• Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
• History of allergy to giredestrant or any of its excipients
• Any condition requiring anti-coagulants, such as warfarin, heparin, or thrombolytic drugs

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (15)

University of Colorado

Aurora, Colorado, 80045-2517, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

Clinique Edith Cavell; Pharmacie

Auderghem, 1160, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Clinique Sainte-Elisabeth; Oncologie

Namur, 5000, Belgium

Location

Onkologikoa - Instituto Oncológico de Donostia

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Ruber Internacional;Servicio de Oncologia

Madrid, 28034, Spain

Location

HM Sanchinarro ? CIOCC

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Barts Health NHS Trust; William Harvey Heart Centre, QMUL School of Medicine & Dentistry

London, EC1M 6BQ, United Kingdom

Location

Royal Cornwall Hospital

Truro, TR1 3LQ, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

giredestrant; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 16, 2019
• Study Start: July 26, 2019
• Primary Completion: May 25, 2021
• Study Completion: May 25, 2021
• Last Updated: March 10, 2023
• Results First Posted: March 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); GB (2); BE (3); AU (2); ES (5)