Clinical trial NCT03916744: A Study of Giredestrant (GDC-9545) in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer
Official title: A Phase I, Multicenter, Open-Label Preoperative, Short-Term Window Study of GDC-9545 in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2019-04-16
Enrollment: 75
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline and Surgery (Day 15)
measure: 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
timeFrame: Baseline and Surgery (Day 15)
Secondary outcomes:
measure: 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)
timeFrame: From Baseline to Day 43
measure: Percentage of Participants With Abnormal Vital Signs During Treatment
timeFrame: Baseline, Days 1, 8, and 15
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)
measure: Change From Baseline in Systolic Blood Pressure
timeFrame: Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)
measure: Change From Baseline in Diastolic Blood Pressure
timeFrame: Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)
measure: Change From Baseline in Body Temperature
timeFrame: Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)
measure: Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline
timeFrame: Baseline, Days 1, 8, and 15
measure: Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline
timeFrame: Baseline, Days 1, 8, and 15
measure: Percentage of Participants With Abnormal Electrocardiogram Parameters During Treatment
timeFrame: Baseline, Days 1, 8, and 15
measure: Plasma Concentration of Giredestrant at Steady State by Dose Level
timeFrame: Predose on day of surgery (Day 15), or prior to biopsy (Day 14)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Auderghem
country: Belgium
facility: Clinique Edith Cavell; Pharmacie
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Namur
country: Belgium
facility: Clinique Sainte-Elisabeth; Oncologie
city: San Sebastian
country: Spain
facility: Onkologikoa - Instituto Oncológico de Donostia
state: Guipuzcoa
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Ruber Internacional;Servicio de Oncologia
city: Madrid
country: Spain
facility: HM Sanchinarro ? CIOCC
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: London
country: United Kingdom
facility: Barts Health NHS Trust; William Harvey Heart Centre, QMUL School of Medicine & Dentistry
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: