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
Overview
- Phase
- Phase 1
- Intervention
- Giredestrant
- Conditions
- Breast Cancer
- Sponsor
- Genentech, Inc.
- Enrollment
- 75
- Locations
- 15
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
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
Arms & Interventions
Giredestrant 10 mg
Intervention: Giredestrant
Giredestrant 10 mg
Intervention: Surgery
Giredestrant 30 mg
Intervention: Giredestrant
Giredestrant 30 mg
Intervention: Surgery
Giredestrant 100 mg
Intervention: Giredestrant
Giredestrant 100 mg
Intervention: Surgery
Outcomes
Primary Outcomes
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
Time Frame: Baseline and Surgery (Day 15)
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).
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
Time Frame: Baseline and Surgery (Day 15)
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).
Secondary Outcomes
- Percentage of Participants With Abnormal Vital Signs During Treatment(Baseline, Days 1, 8, and 15)
- 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)
- 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))
- Change From Baseline in Body Temperature(Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43))
- Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline(Baseline, Days 1, 8, and 15)
- Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline(Baseline, Days 1, 8, and 15)
- Percentage of Participants With Abnormal Electrocardiogram Parameters During Treatment(Baseline, Days 1, 8, and 15)
- Plasma Concentration of Giredestrant at Steady State by Dose Level(Predose on day of surgery (Day 15), or prior to biopsy (Day 14))