A Study of GDC-0927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Genentech, Inc.43 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Cancer

Interventions

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (13)

Massachusetts General Hospital.

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Sarah Cannon Cancer Center

Germantown, Tennessee, United States

Vanderbilt Ingram Cancer Ctr

Nashville, Tennessee, United States

ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO

L'Hospitalet de Llobregat, Barcelona, Spain

Onkologikoa - Kutxaren Institutu Onkologikoa

Donostia / San Sebastian, Guipuzcoa, Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, Spain

MD Anderson Cancer Center Madrid - España; Servicio de Farmacia

Madrid, Spain

Hospital Universitario Ramón y Cajal

Madrid, Spain

...and 3 more locations

Outcomes

Primary Outcomes

Maximum Tolerated Dose (MTD)/Recommended Phase II Dose (RP2D) of GDC-0927

Time frame: Day-7 through Cycle 1 (cycle length: 28 days)

Percentage of Participants With Adverse Events (AEs)

Time frame: From screening up to approximately 3 years

Secondary Outcomes

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)

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)

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)

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)

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)

Part II: Tmax of GDC-0927

Part I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0927

Part II: AUC of GDC-0927

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)

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)

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)

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)

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)

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)