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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02983071
• Other study ID #: G1T38-02
• Secondary ID: 2016-001485-29
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 2017
• Est. completion date: October 2023

Study information

• Verified date: February 2023
• Source: G1 Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: October 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasm
• Breast Neoplasms
• Carcinoma, Ductal
• Carcinoma, Ductal, Breast

Intervention

Drug:
• G1T38

• Fulvestrant

Locations

Country	Name	City	State
Bulgaria	MHAT for Womens Health - Nadezhda OOD	Sofia
Bulgaria	Special Hospital For Active Treatment In Oncology	Sofia
Georgia	ARENSIA Exploratory Medicine LLC	Tbilisi
Moldova, Republic of	The Institute of Oncology	Chisinau
United Kingdom	Cambridge University	Cambridge
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	University College London Hospital (UCLH)	London
United Kingdom	The Christie NHS Foundation	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
G1 Therapeutics, Inc.

Countries where clinical trial is conducted

Bulgaria,  Georgia,  Moldova, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity		Week 1 Day 1-Week 5 Day 1
Primary	Recommended Phase 2 dose		14 months
Primary	Recommended Phase 2 dose interval	Twice-Daily or Once-Daily dosing	14 months
Primary	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	36 months
Secondary	Tumor response based on RECIST, Version 1.1		30 months
Secondary	Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Maximum Plasma Concentration (Cmax)		Week 1 Day 1-Week 9 Day 1
Secondary	Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Area under Curve - plasma concentration (AUC)		Week 1 Day 1-Week 9 Day 1
Secondary	Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma: terminal half life (T1/2)		Week 1 Day 1-Week 9 Day 1
Secondary	Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution		Week 1 Day 1-Week 9 Day 1
Secondary	Progression free survival (PFS)		36 months
Secondary	Overall survival (OS)		48 months