A Study of GDC-0810 Versus Fulvestrant in Postmenopausal Women With Advanced or Metastatic Breast Cancer Resistant to Aromatase Inhibitor (AI) Therapy (HydranGea)

A Phase II, Open-Label, Randomized Study of GDC-0810 Versus Fulvestrant in Postmenopausal Women With Advanced or Metastatic ER+ /HER2- Breast Cancer Resistant to Aromatase Inhibitor Therapy

The primary purpose of this study is to evaluate the efficacy, safety, and tolerability of GDC-0810 compared with fulvestrant in postmenopausal women with advanced or metastatic estrogen receptor positive (ER+)/ human epidermal growth factor receptor 2 negative (HER2-) breast cancer resistant to AI therapy. The development of GDC-0810 has been halted by the Sponsor and the enrollment in this study has been discontinued. Participants currently enrolled in the study who are experiencing clinical benefit may continue receiving GDC-0810 as a single agent or fulvestrant until disease progression (PD), unmanageable toxicity, withdrawal of consent, exhaustion of GDC-0810 drug supply, or termination of the study by the Sponsor.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: GDC-0810

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Port Macquarie, New South Wales, Australia, 2444
      • Port Macquarie Base Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Adelaide Cancer Centre
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital; Medical Oncology
  • Victoria
    • Footscray, Victoria, Australia, 3011
      • Footscray Hospital
    • Frankston, Victoria, Australia, 3199
      • Peninsula and South Eastern Haematology and Oncology Group
    • Richmond, Victoria, Australia, 3121
      • Epworth HealthCare; Clinical Trials Centre
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Koblenz, Germany, 56068
    • Praxisklinik für Hämatologie und Onkologie Dres. Köppler/Heymans/Weide/Thomalla
  • Krefeld, Germany, 47805
    • HELIOS Klinikum Krefeld; Klinik für Frauenheilkunde und Geburtshilfe
  • Muenchen, Germany, 80637
    • Rotkreuzklinikum München; Frauenklinik
  • Tuebingen, Germany, 72076
    • Universitätsklinikum Tübingen
  • Witten, Germany, 58452
    • Marien Hospital Witten Gemeinnützige GmbH
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Medical Center
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, (0)6351
    • Samsung Medical Center
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hosiptal
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28040
    • Hosp. Clinico San Carlos
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Cantabria
    • Barcelona, Cantabria, Spain, 08036
      • Hospital Clinic
  • LA Coruña
    • A Coruña, LA Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña; Servicio de Endocrinologia
  • Lerida
    • Lleida, Lerida, Spain, 25198
      • Hospital Universitari Arnau de Vilanova
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Royal Sussex County Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital
  • London, United Kingdom, N7 9NH
    • University College Hospital
  • Macclesfield, United Kingdom, SK10 3BL
    • Macclesfield District General Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33908
      • Florida Cancer Specialists-Broadway, Fort Myers
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Tennessee Oncology PLLC
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders - Fort Worth
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

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:

• Postmenopausal women with histologically or cytologically confirmed invasive, ER+/HER- (defined by local guidelines) metastatic or inoperable, locally advance breast cancer
• Participants for whom endocrine therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study
• Participants must have measurable disease by RECIST v1.1 or non-measurable, evaluable disease with atleast one evaluable bone lesion by RECIST v1.1 based on radiologic scans within 28 days of Day 1 of Cycle 1
• Participants with radiologic/objective evidence of breast cancer recurrence or progression while on or within 6 months after the end of adjuvant treatment with an AI, or progression while on or within 1 month after the end of prior AI treatment for locally advanced or metastatic breast cancer

Exclusion Criteria:

• HER2-positive disease
• Prior treatment with fulvestrant
• Prior treatment with greater than (>) 1 cytotoxic chemotherapy regimen or >2 endocrine therapies for advanced or metastatic disease

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
Active Comparator: Fulvestrant; Participants will receive 500 milligrams (mg) of fulvestrant as two intramuscular injections (250 mg each) on Day 1 and Day 15 of Cycle 1, and on Day 1 of each subsequent 28-day cycle until disease progression, unmanageable toxicity, withdrawal of consent, exhaustion of GDC-0810 drug supply, or termination of study by the Sponsor.	Drug: Fulvestrant; Fulvestrant at a dose of 500 mg as two intramuscular injections will be administered on Day 1 and Day 15 of Cycle 1, and on Day 1 of each subsequent 28-day cycle.
Experimental: GDC-0810; Participants will receive three 200 mg tablets (total dose = 600 mg) of GDC-0810 orally once daily until disease progression, unmanageable toxicity, withdrawal of consent, exhaustion of GDC-0810 drug supply, or termination of study by the Sponsor.	Drug: GDC-0810; GDC-0810 will be administered as tablets at a dose of 600 mg orally once daily.; Other Names: RO7056118

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Intent-to-Treat (ITT) Population	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1 or death on study from any cause.	From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)
PFS According to RECIST v1.1 in Participants With Estrogen Receptor (ESR)1 Mutations	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1 or death on study from any cause.	From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	From Day 1 to death from any cause, assessed up to end of study (up to approximately 25 months)
Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]) According to RECIST v1.1	Objective Response was defined as the percentage of participants who attained CR or PR. CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)
Duration of Response (DOR) Assessed Using RECIST v1.1	DOR was defined as the time from first observation of an objective response until first observation of disease progression as assessed by the investigator according to RECIST v1.1 or death from any cause.	From objective response to PD or death from any cause, assessed up to end of study (up to approximately 25 months)
Percentage of Participants With Clinical Benefit (PR, CR, or Stable Disease, Lasting for At Least 24 Weeks) Assessed Using RECIST v1.1		From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)		From Day 1 to 28 days after last dose of study drug, assessed up to end of study (up to approximately 25 months)
GDC-0810 Plasma Concentrations by Visit	Concentration of GDC-0810 measured in plasma after a single dose (Cycle 1 Day 1) and at steady state (Cycle 3 Day 1)	Predose (within 30 minutes of GDC-0810 administration) and 3 hours postdose on Day 1 of Cycles 1 and 3; Cycle length=28 days

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2015
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): February 28, 2020

Study Registration Dates

• First Submitted: October 6, 2015
• First Submitted That Met QC Criteria: October 6, 2015
• First Posted (Estimate): October 7, 2015

Study Record Updates

• Last Update Posted (Actual): April 23, 2021
• Last Update Submitted That Met QC Criteria: April 21, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: GO29689; 2015-000106-19 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No