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

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ClinicalTrials.gov Identifier: NCT03455270
Recruitment Status : Recruiting
First Posted : March 6, 2018
Last Update Posted : September 28, 2018
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Carcinoma, Ductal, Breast Breast Cancer Female Breast Neoplasm Breast Cancer Drug: G1T48 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 9, 2018
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Part 1: Dose Escalation

Patients 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.

Drug: G1T48
oral SERD

Experimental: Part 1: Food Effect Cohort

In 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.

Drug: G1T48
oral SERD

Experimental: Part 2: Dose Expansion
Patients in Part 2 will receive G1T48 once-daily at the dose determined in Part 1.
Drug: G1T48
oral SERD




Primary Outcome Measures :
  1. Dose Limiting Toxicity [ Time Frame: Cycle 1 Day -3 to Cycle 1 Day 28 ]
  2. Recommended Phase 2 dose [ Time Frame: 12 months ]
  3. Number of Treatment Related Adverse Event, including Abnormal Laboratory Events [ Time Frame: 21 months ]
    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 :
  1. Tumor response based on RECIST, Version 1.1 [ Time Frame: 21 months ]
  2. Effect of food on bioavailability of G1T48 [ Time Frame: Part 1, Cycle 1 Day -10 to Cycle 1 Day 1. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]
  6. 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. ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03455270


Contacts
Contact: G1 Therapeutics Clinical Contact 919-213-9835 clinicalinfo@g1therapeutics.com

Locations
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7305
Principal Investigator: Carey Anders, MD         
Belgium
Institut Jules Bordet Recruiting
Brussels, Belgium, 1000
Principal Investigator: Philippe Aftimos, MD         
UZ Leuven Recruiting
Leuven, Belgium, 3000
Principal Investigator: Patrick Neven, MD         
Netherlands
VU University Medical Center Recruiting
Amsterdam, Netherlands, 1081 HV
Principal Investigator: C. Willimien Menke, MD         
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Principal Investigator: Elisabeth de Vries, MD         
Erasmus Medical Center Recruiting
Rotterdam, Netherlands, 3015 GD
Principal Investigator: Agnes Jager, MD         
Sponsors and Collaborators
G1 Therapeutics, Inc.
Investigators
Study Director: Clinical Contact G1 Therapeutics, Inc.

Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03455270     History of Changes
Other Study ID Numbers: G1T48-01
2017-004502-17 ( EudraCT Number )
First Posted: March 6, 2018    Key Record Dates
Last Update Posted: September 28, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by G1 Therapeutics, Inc.:
Breast Cancer
Oral SERD
SERD
HER2-Negative
ER-Positive
ER+
HER2-
HER2 -ve
ER +ve

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Ductal
Carcinoma, Ductal, Breast
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Ductal, Lobular, and Medullary