Clinical Trials /

G1T48, an Oral SERD, in ER-Positive, HER2-Negative Advanced Breast Cancer

NCT03455270

Description:

This is a study to investigate the potential clinical benefit of G1T48 as an oral selective estrogen receptor degrader (SERD) in patients with estrogen receptor-positive, HER2-negative metastatic breast cancer. The study is an open-label design, consisting of 2 parts: dose-finding portion (Part 1), and expansion portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 104 patients will be enrolled in the study.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: G1T48, an Oral SERD, in ER-Positive, HER2-Negative Advanced Breast Cancer
  • Official Title: A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Ascending Doses of G1T48 in Women With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: G1T48-01
  • SECONDARY ID: 2017-004502-17
  • NCT ID: NCT03455270

Conditions

  • Carcinoma, Ductal, Breast
  • Breast Cancer Female
  • Breast Neoplasm
  • Breast Cancer

Interventions

DrugSynonymsArms
G1T48Part 1: Dose Escalation

Purpose

This is a study to investigate the potential clinical benefit of G1T48 as an oral selective estrogen receptor degrader (SERD) in patients with estrogen receptor-positive, HER2-negative metastatic breast cancer. The study is an open-label design, consisting of 2 parts: dose-finding portion (Part 1), and expansion portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 96 patients will be enrolled in the study.

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose EscalationExperimentalPatients in Part 1 will receive a single oral dose of G1T48 on Cycle 1 Day -3 and will begin once-daily dosing on Cycle 1 Day 1. The initial dose cohort shall receive an identified starting dose and subsequent cohorts shall receive higher doses based on the safety and PK data obtained from the previous dose levels.
  • G1T48
Part 1: Food Effect CohortExperimentalIn Part 1, an additional G1T48 cohort of 8 patients may be enrolled to assess the effect of a high-fat meal on the rate and extent of the absorption of G1T48. Patients will receive a single oral dose of G1T48 on Cycle 1 Day -10 and on Cycle 1 Day -3. Patients will begin G1T48 once-daily dosing on Cycle 1 Day 1.
  • G1T48
Part 2: Dose ExpansionExperimentalPatients in Part 2 will receive G1T48 once-daily at the dose determined in Part 1.
  • G1T48

Eligibility Criteria

        Inclusion Criteria:

          -  For Part 1, postmenopausal women only

          -  For Part 2, any menopausal status

          -  Confirmed diagnosis of ER-positive, HER2-negative advanced breast cancer, not amenable
             to curative therapy

          -  For Part 1, prior treatment with less than 4 prior lines of chemotherapy

          -  For Part 2, prior treatment with less than 2 prior line of chemotherapy

          -  Prior treatment with less than 4 prior endocrine therapies for metastatic breast
             cancer

          -  Patients must satisfy 1 of the following criteria for prior therapy:

               -  Progressed during treatment or within 12 months of completion of adjuvant therapy
                  with an aromatase inhibitor

               -  Progressed after the end of prior aromatase inhibitor therapy for
                  advanced/metastatic breast cancer

          -  For Part 1, evaluable or measurable disease

          -  For Part 2, measurable disease as defined by RECIST, Version 1.1 including bone-only
             disease

          -  ECOG performance status 0 to 1

          -  Adequate organ function

        Exclusion Criteria:

          -  Prior treatment with SERMs or SERDs within 5 weeks of first G1T48 dose

          -  Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or
             leptomeningeal disease

          -  Anticancer therapy within 14 days of first G1T48 dose or within 28 days for
             antibody-based therapy

          -  Concurrent radiotherapy, radiotherapy within 14 days of first G1T48 dose, previous
             radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow

          -  Prior hematopoietic stem cell or bone marrow transplantation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:Cycle 1 Day -3 to Cycle 1 Day 28
Safety Issue:
Description:All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all patients receiving study drug from the signing of the informed consent until 30 days after the last dose of study medication.

Secondary Outcome Measures

Measure:Tumor response based on RECIST, Version 1.1
Time Frame:21 months
Safety Issue:
Description:
Measure:Effect of food on bioavailability of G1T48
Time Frame:Part 1, Cycle 1 Day -10 to Cycle 1 Day 1.
Safety Issue:
Description:
Measure:Pharmacokinetics of G1T48 and metabolites: Maximum Plasma Concentration (Cmax)
Time Frame:Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1.
Safety Issue:
Description:
Measure:Pharmacokinetics of G1T48 and metabolites: Area under Curve - plasma concentration (AUC)
Time Frame:Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1.
Safety Issue:
Description:
Measure:Pharmacokinetics of G1T48 and metabolites: Plasma: terminal half life (T1/2)
Time Frame:Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1.
Safety Issue:
Description:
Measure:Pharmacokinetics of G1T48 and metabolites: Plasma - Volume of distribution
Time Frame:Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1.
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:G1 Therapeutics, Inc.

Trial Keywords

  • Breast Cancer
  • Oral SERD
  • SERD
  • HER2-Negative
  • ER-Positive
  • ER+
  • HER2-
  • HER2 -ve
  • ER +ve

Last Updated