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

An Open-Label, Phase I Study of GDC-0927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

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 Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: GDC-0927

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center Madrid - España; Servicio de Farmacia
  • Madrid, Spain, 28040
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28050
    • HM Sanchinarro - CIOCC
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
  • Guipuzcoa
    • San Sebastian, Guipuzcoa, Spain, 20014
      • Onkologikoa - Kutxaren Institutu Onkologikoa
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital.
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Sarah Cannon Cancer Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Ctr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I: Dose Escalation - GDC-0927; 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.	Drug: GDC-0927; GDC-0927 will be administered as per schedule specified in the respective arm.; Other Names: RO7056119
Experimental: Part II: Dose Expansion - GDC-0927; 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.	Drug: GDC-0927; GDC-0927 will be administered as per schedule specified in the respective arm.; Other Names: RO7056119

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose (MTD)/Recommended Phase II Dose (RP2D) of GDC-0927	Day-7 through Cycle 1 (cycle length: 28 days)
Percentage of Participants With Adverse Events (AEs)	From screening up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Objective Response Assessed by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)	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	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	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	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	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	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: Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0927	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: AUC of GDC-0927	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)
Plasma Half-Life (t1/2) of GDC-0927	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	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)	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	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	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	Screening (baseline); Cycle 1 Day 1; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: Seragon Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2015
• Primary Completion (Actual): January 10, 2020
• Study Completion (Actual): January 10, 2020

Study Registration Dates

• First Submitted: December 4, 2014
• First Submitted That Met QC Criteria: December 10, 2014
• First Posted (Estimate): December 15, 2014

Study Record Updates

• Last Update Posted (Actual): October 5, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: GO29656; 2015-000272-95 (EudraCT Number)