G1T38, a CDK 4/6 Inhibitor, in Combination With Fulvestrant in Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
Primary Purpose
Carcinoma, Ductal, Breast, Breast Cancer, Breast Neoplasm
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
G1T38
Fulvestrant
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Ductal, Breast focused on measuring Breast Cancer, CDK 4/6 Inhibitor, HER2-Negative, HR-Positive, HR+, HER2-, HER2 -ve, HER2 +ve
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of HR-positive, HER2-negative breast cancer, not amenable to curative therapy
- Pre- or perimenopausal women can be enrolled if amenable to be treated with goserelin
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 or tamoxifen
- Progressed during treatment or within 2 months after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer, or prior endocrine therapy for advanced/metastatic breast cancer
- Received ≤ 2 chemotherapy regimens (Part 1) or ≤ 1 chemotherapy regimen (Part 2) for advanced/metastatic disease
- For Part 1, evaluable or measurable disease (bone only disease eligible for Part 1 only)
- For Part 2, measurable disease as defined by RECIST, Version 1.1
- ECOG performance status 0 to 1
- Adequate organ function
Exclusion Criteria:
- For Part 1, prior treatment with fulvestrant
- For Part 2, prior treatment with any CDK inhibitor or fulvestrant
- Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
- Chemotherapy within 21 days of first G1T38 dose
- Investigational drug within 28 days of first G1T38 dose
- Concurrent radiotherapy, radiotherapy within 14 days of first G1T38 dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow
- Prior hematopoietic stem cell or bone marrow transplantation
Sites / Locations
- MHAT for Womens Health - Nadezhda OOD
- Special Hospital For Active Treatment In Oncology
- ARENSIA Exploratory Medicine LLC
- The Institute of Oncology
- Cambridge University
- University College London Hospital (UCLH)
- Sarah Cannon Research Institute
- The Christie NHS Foundation
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Once-Daily G1T38 Dosing
Twice-Daily G1T38 Dosing
Arm Description
G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.
G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.
Outcomes
Primary Outcome Measures
Dose Limiting Toxicity
Recommended Phase 2 dose
Recommended Phase 2 dose interval
Twice-Daily or Once-Daily dosing
Number of Treatment Related Adverse Event, including Abnormal Laboratory Events
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 up to 36 months
Secondary Outcome Measures
Tumor response based on RECIST, Version 1.1
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Maximum Plasma Concentration (Cmax)
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Area under Curve - plasma concentration (AUC)
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma: terminal half life (T1/2)
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution
Progression free survival (PFS)
Overall survival (OS)
Full Information
NCT ID
NCT02983071
First Posted
November 29, 2016
Last Updated
February 14, 2023
Sponsor
G1 Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02983071
Brief Title
G1T38, a CDK 4/6 Inhibitor, in Combination With Fulvestrant in Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
Official Title
Phase 1/2 Safety, Pharmacokinetic, and Antitumor Activity Study of G1T38 in Combination With Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer After Endocrine Failure
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2017 (undefined)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
G1 Therapeutics, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a study to investigate the potential clinical benefit of G1T38 as an oral therapy in combination with fulvestrant in patients with hormone receptor-positive, HER2-negative metastatic breast cancer.
The study is an open-label design, consists 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, 102 patients will be enrolled in the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Ductal, Breast, Breast Cancer, Breast Neoplasm
Keywords
Breast Cancer, CDK 4/6 Inhibitor, HER2-Negative, HR-Positive, HR+, HER2-, HER2 -ve, HER2 +ve
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
102 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Once-Daily G1T38 Dosing
Arm Type
Experimental
Arm Description
G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.
Arm Title
Twice-Daily G1T38 Dosing
Arm Type
Experimental
Arm Description
G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.
Intervention Type
Drug
Intervention Name(s)
G1T38
Other Intervention Name(s)
lerociclib
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Other Intervention Name(s)
Faslodex
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity
Time Frame
Week 1 Day 1-Week 5 Day 1
Title
Recommended Phase 2 dose
Time Frame
14 months
Title
Recommended Phase 2 dose interval
Description
Twice-Daily or Once-Daily dosing
Time Frame
14 months
Title
Number of Treatment Related Adverse Event, including Abnormal Laboratory Events
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 up to 36 months
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Tumor response based on RECIST, Version 1.1
Time Frame
30 months
Title
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Maximum Plasma Concentration (Cmax)
Time Frame
Week 1 Day 1-Week 9 Day 1
Title
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Area under Curve - plasma concentration (AUC)
Time Frame
Week 1 Day 1-Week 9 Day 1
Title
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma: terminal half life (T1/2)
Time Frame
Week 1 Day 1-Week 9 Day 1
Title
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution
Time Frame
Week 1 Day 1-Week 9 Day 1
Title
Progression free survival (PFS)
Time Frame
36 months
Title
Overall survival (OS)
Time Frame
48 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of HR-positive, HER2-negative breast cancer, not amenable to curative therapy
Pre- or perimenopausal women can be enrolled if amenable to be treated with goserelin
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 or tamoxifen
Progressed during treatment or within 2 months after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer, or prior endocrine therapy for advanced/metastatic breast cancer
Received ≤ 2 chemotherapy regimens (Part 1) or ≤ 1 chemotherapy regimen (Part 2) for advanced/metastatic disease
For Part 1, evaluable or measurable disease (bone only disease eligible for Part 1 only)
For Part 2, measurable disease as defined by RECIST, Version 1.1
ECOG performance status 0 to 1
Adequate organ function
Exclusion Criteria:
For Part 1, prior treatment with fulvestrant
For Part 2, prior treatment with any CDK inhibitor or fulvestrant
Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
Chemotherapy within 21 days of first G1T38 dose
Investigational drug within 28 days of first G1T38 dose
Concurrent radiotherapy, radiotherapy within 14 days of first G1T38 dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow
Prior hematopoietic stem cell or bone marrow transplantation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Contact
Organizational Affiliation
G1 Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
MHAT for Womens Health - Nadezhda OOD
City
Sofia
ZIP/Postal Code
1330
Country
Bulgaria
Facility Name
Special Hospital For Active Treatment In Oncology
City
Sofia
ZIP/Postal Code
1756
Country
Bulgaria
Facility Name
ARENSIA Exploratory Medicine LLC
City
Tbilisi
ZIP/Postal Code
0112
Country
Georgia
Facility Name
The Institute of Oncology
City
Chisinau
ZIP/Postal Code
2025
Country
Moldova, Republic of
Facility Name
Cambridge University
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
University College London Hospital (UCLH)
City
London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Facility Name
Sarah Cannon Research Institute
City
London
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
Facility Name
The Christie NHS Foundation
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
G1T38, a CDK 4/6 Inhibitor, in Combination With Fulvestrant in Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
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