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

Phase 1

Active, not recruiting

• Conditions: Carcinoma, Ductal, Breast; Breast Neoplasm; Breast Cancer
• Interventions: Drug: G1T38; Drug: Fulvestrant

• Registration Number: NCT02983071
• Lead Sponsor: G1 Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-11-29
• Study First Submitted QC: 2016-12-01
• Study First Posted: 2016-12-06
• Study Start: 2017-01
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-14
• Last Update Posted: 2023-02-15
• Primary Completion: 2023-06
• Study Completion: 2023-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 102

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Once-Daily G1T38 Dosing	G1T38	G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.
Twice-Daily G1T38 Dosing	G1T38	G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.
Once-Daily G1T38 Dosing	Fulvestrant	G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.
Twice-Daily G1T38 Dosing	Fulvestrant	G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.

Primary Outcome Measures

Name	Time	Method
Recommended Phase 2 dose	14 months
Recommended Phase 2 dose interval	14 months	Twice-Daily or Once-Daily dosing
Dose Limiting Toxicity	Week 1 Day 1-Week 5 Day 1
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

Name	Time	Method
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: Plasma: terminal half life (T1/2)	Week 1 Day 1-Week 9 Day 1
Overall survival (OS)	48 months
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 - Volume of distribution	Week 1 Day 1-Week 9 Day 1
Progression free survival (PFS)	36 months

Trial Locations

Locations (8)

Special Hospital For Active Treatment In Oncology; 🇧🇬 Sofia, Bulgaria

MHAT for Womens Health - Nadezhda OOD; 🇧🇬 Sofia, Bulgaria

The Institute of Oncology; 🇲🇩 Chisinau, Moldova, Republic of

University College London Hospital (UCLH); 🇬🇧 London, United Kingdom

Sarah Cannon Research Institute; 🇬🇧 London, United Kingdom

Cambridge University; 🇬🇧 Cambridge, United Kingdom

The Christie NHS Foundation; 🇬🇧 Manchester, United Kingdom

ARENSIA Exploratory Medicine LLC; 🇬🇪 Tbilisi, Georgia