Breast Cancer, Breast Neoplasm, Carcinoma, Ductal, Breast
Conditions
Keywords
Breast Cancer, CDK 4/6 Inhibitor, HER2-Negative, HR-Positive, HR+, HER2-, HER2 -ve, HER2 +ve
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.
Interventions
DRUGG1T38
DRUGFulvestrant
Sponsors
G1 Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution | Week 1 Day 1-Week 9 Day 1 |
| Tumor response based on RECIST, Version 1.1 | 30 months |
| Overall survival (OS) | 48 months |
| Progression free survival (PFS) | 36 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 |
Countries
Bulgaria, Georgia, Moldova, United Kingdom
Outcome results
None listed