G1T38, a CDK 4/6 Inhibitor, in Combination With Fulvestrant in Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

Sponsor

G1 Therapeutics, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02983071

Collaborator

(none)

102

Enrollment

Locations

Arms

74.9

Duration (Months)

12.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Ductal, Breast Breast Cancer Breast Neoplasm	Drug: G1T38 Drug: Fulvestrant	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

102 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Once-Daily G1T38 Dosing G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.	Drug: G1T38 Other Names: lerociclib Drug: Fulvestrant Other Names: Faslodex
Experimental: Twice-Daily G1T38 Dosing G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.	Drug: G1T38 Other Names: lerociclib Drug: Fulvestrant Other Names: Faslodex

Arm

Intervention/Treatment

Experimental: Once-Daily G1T38 Dosing

G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.

Drug: G1T38

Other Names:

lerociclib

Drug: Fulvestrant

Other Names:

Faslodex

Experimental: Twice-Daily G1T38 Dosing

G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.

Drug: G1T38

Other Names:

lerociclib

Drug: Fulvestrant

Other Names:

Faslodex

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicity [Week 1 Day 1-Week 5 Day 1]
Recommended Phase 2 dose [14 months]
Recommended Phase 2 dose interval [14 months]
Twice-Daily or Once-Daily dosing
Number of Treatment Related Adverse Event, including Abnormal Laboratory Events [36 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 up to 36 months

Secondary Outcome Measures

Tumor response based on RECIST, Version 1.1 [30 months]
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Maximum Plasma Concentration (Cmax) [Week 1 Day 1-Week 9 Day 1]
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Area under Curve - plasma concentration (AUC) [Week 1 Day 1-Week 9 Day 1]
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma: terminal half life (T1/2) [Week 1 Day 1-Week 9 Day 1]
Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution [Week 1 Day 1-Week 9 Day 1]
Progression free survival (PFS) [36 months]
Overall survival (OS) [48 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	MHAT for Womens Health - Nadezhda OOD	Sofia	Bulgaria	1330
2	Special Hospital For Active Treatment In Oncology	Sofia	Bulgaria	1756
3	ARENSIA Exploratory Medicine LLC	Tbilisi	Georgia	0112
4	The Institute of Oncology	Chisinau	Moldova, Republic of	2025
5	Cambridge University	Cambridge	United Kingdom	CB2 0QQ
6	University College London Hospital (UCLH)	London	United Kingdom	NW1 2BU
7	Sarah Cannon Research Institute	London	United Kingdom	W1G 6AD
8	The Christie NHS Foundation	Manchester	United Kingdom	M20 4BX