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

NCT02983071 | Unknown Phase 1 DMC

• 2 other identifiers: G1T38-022016-001485-29
• Study Type: interventional
• Target: 102
• Locations: 4 countries
• Sites: 8

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.

Conditions

Carcinoma, Ductal, Breast; Breast Cancer; Breast Neoplasm

Keywords

Breast Cancer; CDK 4/6 Inhibitor; HER2-Negative; HR-Positive; HR+; HER2-; HER2 -ve; HER2 +ve

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicity

  Week 1 Day 1-Week 5 Day 1

• Recommended Phase 2 dose

  14 months

• Recommended Phase 2 dose interval

  Twice-Daily or Once-Daily dosing

  14 months

• 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 Outcomes (7)

• 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

Study Arms (2)

Once-Daily G1T38 Dosing

EXPERIMENTAL

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

Drug: G1T38; Drug: Fulvestrant

Twice-Daily G1T38 Dosing

EXPERIMENTAL

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

Drug: G1T38; Drug: Fulvestrant

Interventions

G1T38 DRUG

Also known as: lerociclib

Once-Daily G1T38 Dosing; Twice-Daily G1T38 Dosing

Fulvestrant DRUG

Also known as: Faslodex

Once-Daily G1T38 Dosing; Twice-Daily G1T38 Dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (8)

MHAT for Womens Health - Nadezhda OOD

Sofia, 1330, Bulgaria

Location

Special Hospital For Active Treatment In Oncology

Sofia, 1756, Bulgaria

Location

ARENSIA Exploratory Medicine LLC

Tbilisi, 0112, Georgia

Location

The Institute of Oncology

Chisinau, 2025, Moldova

Location

Cambridge University

Cambridge, CB2 0QQ, United Kingdom

Location

University College London Hospital (UCLH)

London, NW1 2BU, United Kingdom

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

The Christie NHS Foundation

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Ductal, Breast; Breast Neoplasms

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Clinical Contact

  G1 Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 6, 2016
• Study Start: January 1, 2017
• Primary Completion: June 1, 2023
• Study Completion: October 1, 2023
• Last Updated: February 15, 2023

Record last verified: 2023-02

Locations

BU (2); GE (1); GB (4); MO (1)