Clinical trial NCT02983071: G1T38, a CDK 4/6 Inhibitor, in Combination With Fulvestrant in Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
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
Lead sponsor: G1 Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-12-06
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Dose Limiting Toxicity
timeFrame: Week 1 Day 1-Week 5 Day 1
measure: Recommended Phase 2 dose
timeFrame: 14 months
measure: Recommended Phase 2 dose interval
timeFrame: 14 months
measure: Number of Treatment Related Adverse Event, including Abnormal Laboratory Events
timeFrame: 36 months
Secondary outcomes:
measure: Tumor response based on RECIST, Version 1.1
timeFrame: 30 months
measure: Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Maximum Plasma Concentration (Cmax)
timeFrame: Week 1 Day 1-Week 9 Day 1
measure: Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Area under Curve - plasma concentration (AUC)
timeFrame: Week 1 Day 1-Week 9 Day 1
measure: Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma: terminal half life (T1/2)
timeFrame: Week 1 Day 1-Week 9 Day 1
measure: Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution
timeFrame: Week 1 Day 1-Week 9 Day 1
measure: Progression free survival (PFS)
timeFrame: 36 months
measure: Overall survival (OS)
timeFrame: 48 months
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: MHAT for Womens Health - Nadezhda OOD
city: Sofia
country: Bulgaria
facility: Special Hospital For Active Treatment In Oncology
city: Tbilisi
country: Georgia
facility: ARENSIA Exploratory Medicine LLC
city: Chisinau
country: Moldova, Republic of
facility: The Institute of Oncology
city: Cambridge
country: United Kingdom
facility: Cambridge University
city: London
country: United Kingdom
facility: University College London Hospital (UCLH)
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation
Study officials:
affiliation: G1 Therapeutics, Inc.
name: Clinical Contact
role: STUDY_DIRECTOR
References: