Description:
This is an open-label, dose-finding, safety, pharmacokinetics (PK), and evidence-of-activity
study of GDC-0927 in postmenopausal women with locally advanced or metastatic Estrogen
Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 (HER2) breast cancer. The
study will be conducted in two parts: Dose escalation and Dose expansion. During dose
escalation, GDC-0927 will be administered orally as a single dose on Day -7 for PK evaluation
during the lead-in period. Depending on safety and tolerability, participants will be
assigned sequentially to escalating doses of GDC-0927 using standard 3+3 design. During dose
expansion, there will be no PK week lead-in period. All participants will be treated until
disease progression, unacceptable toxicity, participant withdrawal of consent or study
termination.
Title
- Brief Title: A Study of GDC-0927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer
- Official Title: An Open-Label, Phase I Study of GDC-0927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
GO29656
- SECONDARY ID:
2015-000272-95
- NCT ID:
NCT02316509
Conditions
Interventions
Drug | Synonyms | Arms |
---|
GDC-0927 | RO7056119 | Part I: Dose Escalation - GDC-0927 |
Purpose
This is an open-label, dose-finding, safety, pharmacokinetics (PK), and evidence-of-activity
study of GDC-0927 in postmenopausal women with locally advanced or metastatic Estrogen
Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 (HER2) breast cancer. The
study will be conducted in two parts: Dose escalation and Dose expansion. During dose
escalation, GDC-0927 will be administered orally as a single dose on Day -7 for PK evaluation
during the lead-in period. Depending on safety and tolerability, participants will be
assigned sequentially to escalating doses of GDC-0927 using standard 3+3 design. During dose
expansion, there will be no PK week lead-in period. All participants will be treated until
disease progression, unacceptable toxicity, participant withdrawal of consent or study
termination.
Trial Arms
Name | Type | Description | Interventions |
---|
Part I: Dose Escalation - GDC-0927 | Experimental | Participants will receive GDC-0927 orally as a single dose on Day -7. Continuous daily dosing will commence on Day 1. Depending on safety and tolerability, participants will be assigned sequentially to escalating doses of GDC-0927 with use of a standard 3 + 3 design. The starting dose will be 600 milligrams per day (mg/day), followed by dose escalation in 400 milligrams (mg) increments. | |
Part II: Dose Expansion - GDC-0927 | Experimental | Participants in the expansion cohorts will receive GDC-0927 at MTD/RP2D starting from Day 1 of Cycle 1 (cycle length: 28 days) up to disease progression, unacceptable toxicity, participant withdrawal of consent or study termination. | |
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with
evidence of either locally recurrent disease not amenable to resection or radiation
therapy with curative intent, or metastatic disease, both progressing after at least 6
months of hormonal therapy for ER+ breast cancer
- ER-positive tumor, HER2-negative breast cancer
- No prior treatment with GDC-0810 (allowed only during dose expansion stage)
- No more than 2 prior chemotherapies in the advanced or metastatic setting
- At least 2 months must have elapsed from the use of tamoxifen
- At least 6 months must have elapsed from the use of fulvestrant
- At least 2 weeks must have elapsed from the use of any other endocrine therapy
- At least 3 weeks must have elapsed from the use of any chemotherapy
- Females, 18 years of age or older
- Postmenopausal status as defined by the protocol
- Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to
(</=) 2 (for dose-escalation part) and 0 or 1 (for dose-expansion part)
- Adequate organ function
Exclusion Criteria:
- Untreated or symptomatic brain metastases
- Current treatment with any systemic anti-cancer therapies for advanced disease or any
systemic experimental treatment on another clinical trial
- Any of the following within 12 months prior to enrollment: myocardial infarction,
severe/unstable angina, ongoing cardiac dysrhythmias of Grade greater than or equal to
(>/=) 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft,
symptomatic congestive heart failure, or cerebrovascular accident including transient
ischemic attack
- Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper
gastrointestinal surgery including gastric resection
- Known Human Immunodeficiency Virus (HIV) infection
- Major surgery within 4 weeks prior to enrollment
- Radiation therapy within 2 weeks prior to enrollment
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum Tolerated Dose (MTD)/Recommended Phase II Dose (RP2D) of GDC-0927 |
Time Frame: | Day-7 through Cycle 1 (cycle length: 28 days) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Percentage of Participants With Objective Response Assessed by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) |
Time Frame: | At screening, every 8 weeks from Cycle 1 (each cycle: 28 days) up to end of treatment (up to approximately 3 years) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants With Clinical Benefit Assessed by RECIST v1.1 |
Time Frame: | At screening, every 8 weeks from Cycle 1 (each cycle: 28 days) up to end of treatment (up to approximately 3 years) |
Safety Issue: | |
Description: | |
Measure: | Part I: Maximum Observed Plasma Concentration (Cmax) of GDC-0927 |
Time Frame: | Pre-dose (0 hour [hr]), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day -7; Days -5, -4, -3; pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (cycle length: 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part II: Cmax of GDC-0927 |
Time Frame: | Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (each cycle: 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part I: Time to Reach Cmax (Tmax) of GDC-0927 |
Time Frame: | Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day -7; Days -5, -4, -3; pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (cycle length: 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part II: Tmax of GDC-0927 |
Time Frame: | Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (each cycle: 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0927 |
Time Frame: | Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day -7; Days -5, -4, -3; pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (cycle length: 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part II: AUC of GDC-0927 |
Time Frame: | Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (each cycle: 28 days) |
Safety Issue: | |
Description: | |
Measure: | Plasma Half-Life (t1/2) of GDC-0927 |
Time Frame: | Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day -7; Days -5, -4, -3; pre-dose (0 hr) on Day 1 Cycle 1 (cycle length: 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part II: t1/2 of GDC-0927 |
Time Frame: | Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day 1 Cycle 1 (each cycle: 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part I: Change From Baseline in Corrected QT (QTc) Interval Using Fridericia's Formula, as Assessed by Electrocardiogram (ECG) |
Time Frame: | Screening (baseline); Days -7, -5, -4, -3; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part II: Change From Baseline in QTc Interval Using Fridericia's Formula, as Assessed by ECG |
Time Frame: | Screening (baseline); Cycle 1 Day 1; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part I: Change From Baseline in RR Interval, as Assessed by ECG |
Time Frame: | Screening (baseline); Days -7, -5, -4, -3; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days) |
Safety Issue: | |
Description: | |
Measure: | Part II: Change From Baseline in RR Interval, as Assessed by ECG |
Time Frame: | Screening (baseline); Cycle 1 Day 1; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Genentech, Inc. |
Last Updated
October 5, 2020