Clinical trial NCT03455270: G1T48, an Oral SERD, Alone and in Combination With Palbociclib in ER-Positive, HER2-Negative Advanced Breast Cancer
Official title: A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Ascending Doses of G1T48 Alone and in Combination With Palbociclib in Women With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Ductal, Breast
Breast Cancer Female
Breast Neoplasm
Breast Cancer
Metastatic Breast Cancer
Advanced Breast Cancer
Stage IV Breast Cancer
Keywords: Breast Cancer
Oral SERD
SERD
HER2-Negative
ER-Positive
ER+
HER2-
HER2 -ve
ER +ve
CDK 4/6 Inhibitor
Rintodestrant
G1T48
Lead sponsor: G1 Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-03-06
Enrollment: 107
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a study to investigate the potential clinical benefit of G1T48 as an oral selective estrogen receptor degrader (SERD) alone and in combination with palbociclib, a cyclin dependent kinase 4/6 (CDK 4/6) inhibitor, in patients with estrogen receptor-positive, HER2-negative metastatic breast cancer.

The study is an open-label design, consisting of 3 parts: dose-finding portion including food effect (Part 1), G1T48 monotherapy expansion portion (Part 2), and G1T48 in combination with palbociclib expansion portion (Part 3). All 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, 184 patients may be enrolled in the study.


Eligibility criteria: Inclusion Criteria:

* For Part 1, postmenopausal women only
* For Parts 2 and 3, any menopausal status
* Confirmed diagnosis of ER-positive, HER2-negative advanced breast cancer, not amenable to curative therapy
* For Part 1, prior treatment with less than 4 prior lines of chemotherapy
* For Part 2, prior treatment with less than 2 prior line of chemotherapy
* For Part 3, prior treatment with no more than 1 prior line of chemotherapy
* For Parts 1 and 2, prior treatment with less than 4 prior endocrine therapies for metastatic breast cancer
* For Part 3, prior treatment with no more than 1 prior line of endocrine therapies for metastatic breast cancer
* For Parts 1 and 2, 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
  * Progressed after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer
* For Part 3, patients must satisfy 1 of the following criteria for prior therapy:

  * Received ≥ 24 months of endocrine therapy in the adjuvant setting prior to recurrence or progression
  * Received ≥ 6 months of endocrine therapy in the advanced/metastatic setting prior to progression
* For Part 1, evaluable or measurable disease
* For Parts 2 and 3, evaluable (approximately 25%) or measurable disease (approximately 75%) as defined by RECIST, Version 1.1 including bone-only disease
* ECOG performance status 0 to 1
* Adequate organ function

Exclusion Criteria:

* For Part 3, prior treatment with CDK4/6 inhibitor, investigational oral SERDs or SERCAs in any setting
* Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
* Anticancer therapy within 14 days of first G1T48 dose or within 28 days for antibody-based therapy
* Concurrent radiotherapy, radiotherapy within 14 days of first G1T48 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: Cycle 1 Day -3 to Cycle 1 Day 28
measure: Recommended Phase 2 dose
timeFrame: 12 months
measure: Number of Treatment Related Adverse Event, including Abnormal Laboratory Events
timeFrame: 21 months
Secondary outcomes:
measure: Tumor response based on RECIST, Version 1.1
timeFrame: 21 months
measure: Effect of food on bioavailability of G1T48
timeFrame: Part 1, Cycle 1 Day -10 to Cycle 1 Day 1.
measure: Pharmacokinetics of G1T48 and metabolites: Maximum Plasma Concentration (Cmax)
timeFrame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.
measure: Pharmacokinetics of G1T48 and metabolites: Area under Curve - plasma concentration (AUC)
timeFrame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.
measure: Pharmacokinetics of G1T48 and metabolites: Plasma: terminal half life (T1/2)
timeFrame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.
measure: Pharmacokinetics of G1T48 and metabolites: Plasma - Volume of distribution
timeFrame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.
measure: Pharmacokinetics of palbociclib: Plasma - Trough concentration
timeFrame: Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Women Cancer Center
state: California
city: Chicago
country: United States
facility: Northwestern University - Feinberg School of Medicine
state: Illinois
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology
state: Tennessee
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: UZ Leuven
city: Sofia
country: Bulgaria
facility: MHAT for Womens Health - Nadezhda OOD
city: Tbilisi
country: Georgia
facility: ARENSIA Exploratory Medicine LLC
city: Chisinau
country: Moldova, Republic of
facility: ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Kiev
country: Ukraine
facility: Spizhenko Clinic
Study officials:
affiliation: G1 Therapeutics, Inc.
name: Clinical Contact
role: STUDY_DIRECTOR
References: