A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer

Description

This study will evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD) activity, and preliminary anti-tumor activity of GDC-9545 as a single agent and in combination with palbociclib and/or luteinizing hormone?releasing hormone (LHRH) agonist in patients with advanced or metastatic estrogen receptor (ER)-positive (human epidermal growth factor receptor 2 [HER2]-negative) breast cancer.

Study Start Date

November, 17 2017

Estimated Completion Date

November 2020

Interventions

  • Drug: GDC-9545
  • Drug: LHRH agonist
  • Drug: Palbociclib

Study ID

Genentech, Inc. -- GO39932

Status

Recruiting

Trial ID

NCT03332797

Study Type

Interventional

Trial Phase

Phase 1

Enrollment Quota

130

Sponsor

Genentech, Inc.

Inclusion Criteria for Dose Escalation:
  • 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 with metastatic disease
  • ER-positive tumor
  • HER2-negative breast cancer as per local laboratory testing
  • Measurable disease, or evaluable bone disease
  • that is, bone lesions that are lytic or mixed (lytic + sclerotic) in the absence of measurable lesion
  • Required paired pre
  • and on-treatment tumor biopsies for participants with metastases that are safely accessible as determined by the investigator
  • Advanced or metastatic ER-positive/HER2-negative breast cancer that has recurred or progressed while being treated with adjuvant endocrine therapy for a duration of at least 24 months and/or endocrine therapy in the incurable, locally advanced, or metastatic setting and derived a clinical benefit from therapy (i.e., tumor response or stable disease for at least 6 months)
  • No more than 2 prior lines of treatment for advanced or metastatic breast cancer
  • ? 2 weeks must have elapsed from the use of any other endocrine, targeted therapy or chemotherapy
  • Cohort B0: No prior treatment with Cyclin-Dependent Kinase (CDK) 4/6 inhibitor
  • For participants undergoing 18F-fluoroestradiol (FES) positron emission tomography (PET) imaging additional restrictions on prior therapy include: ? 2 months must have elapsed from the use of tamoxifen
  • ? 6 months must have elapsed from the use of fulvestrant
  • Postmenopausal status
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ? 1
  • Resolution of all acute toxic effects of prior therapy or surgical procedures to baseline or Grade ? 1 (except alopecia or other toxicities not considered to be a safety risk for the patient)
  • Life expectancy of ? 12 weeks
  • Adequate organ function Inclusion Criteria for Dose Expansion: Same as above, except:
  • No more than one prior line of treatment for advanced or metastatic breast cancer
  • Advanced or metastatic disease that is either refractory to or intolerant of existing standard therapy or for which no effective standard therapy that confers clinical benefit is available And plus:
  • Cohort B1?2: No prior treatment with CDK4/6 inhibitor
  • Cohorts A1, A3, and B1 only: Postmenopausal status
  • Cohorts A2, A4, and B2 only: Participants not defined as post-menopausal
  • No prior treatment with an oral selective estrogen receptor degrader (SERD)
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use non-hormonal contraceptive methods with a failure rate of < 1% per year during the treatment period and for 40 days after the last dose of GDC-9545 Exclusion Criteria for Dose Escalation:
  • Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms.
  • Current treatment with any systemic anti-cancer therapies for advanced disease
  • Concurrent treatment with warfarin or phenytoin
  • 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, chronic diarrhea, short bowel syndrome, or major upper GI surgery including gastric resection
  • Known Human Immunodeficiency Virus (HIV) infection
  • Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis (e.g., hepatitis B or hepatitis C virus), current alcohol abuse, or cirrhosis
  • Major surgery within 4 weeks prior to enrollment
  • Radiation therapy within 2 weeks prior to enrollment Exclusion Criteria for Dose Expansion: Same as above, plus:
  • Pregnant, lactating, or breastfeeding
  • Additional exclusion criteria for participants in Cohort B: History of venous thromboembolic event requiring therapeutic anticoagulation
  • Gender

    Female

    Ages

    18 Years and older

    Accepts Healthy Volunteers

    No

    Study Locations and Contact Information (13)

    Study Location Distance Name Phone Email
    Dana Farber Cancer Institute - Boston, Massachusetts 2.4 miles None None None
    Beth Israel Deaconess Medical Center - Boston, Massachusetts 2.4 miles None None None
    Massachusetts General Hospital - Boston, Massachusetts 2.8 miles None None None
    Massachusetts General Hospital - Boston, Massachusetts 2.8 miles None None None
    Massachusetts General Hospital - Boston, Massachusetts 2.8 miles None None None
    Massachusetts General Hospital - Boston, Massachusetts 2.8 miles None None None
    Massachusetts General Hospital - Boston, Massachusetts 2.8 miles None None None
    Memorial Sloan Kettering Cancer Center - New York, New York 187.1 miles None None None
    Vanderbilt University Medical Center Vanderbilt University - Nashville, Tennessee 944.2 miles None None None
    Vanderbilt University Medical Center Vanderbilt University - Nashville, Tennessee 944.2 miles None None None
    Vanderbilt University Medical Center Vanderbilt University - Nashville, Tennessee 944.2 miles None None None
    Vanderbilt University Medical Center Vanderbilt University - Nashville, Tennessee 944.2 miles None None None
    Vanderbilt University Medical Center Vanderbilt University - Nashville, Tennessee 944.2 miles None None None

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