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

Genentech

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Treatments

Drug: Giredestrant

Procedure: Surgery

Study type

Interventional

Funder types

Industry

Identifiers

NCT03916744

GO40987

2018-003798-85 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment

75 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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
History of documented hemorrhagic diathesis or coagulopathy
History or presence of symptomatic bradycardia or sick sinus syndrome
Baseline heart rate ≤55 beats per minute (bpm) prior to enrollment
History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction
QT interval corrected through use of Fridericia's formula (QTcF) >470 milliseconds demonstrated by at least two ECGs >30 minutes apart
History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome
Current treatment with medications that are well known to prolong the QT interval
History or presence of uncontrolled hypothyroidism
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives 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 render the patient at high risk from treatment complications