This is a multicenter, open label, nonrandomized, sequential dose escalation/dose ranging, multiple dose study designed to evaluate the safety, toxicity, and PK as well as preliminary efficacy of BTX-A51 alone and in combination with fulvestrant in subjects with advanced solid tumors. The study will be done in three phases, described below. Phase 1a (Dose Escalation Phase): The Phase 1a portion is designed to determine the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of orally administered BTX-A51. BTX-A51 will be administered once daily on a weekly schedule of 5 days on/2 days off. Dose escalation will proceed according to a modified 3+3 design. Each cycle will consist of 28 days (4 weeks), and the DLT observation period will be the first cycle (i.e., 28 days after initiation of dosing). A DLT may be observed in no more than 0 out of 3 or 1 out of 6 subjects who have completed the DLT observation period before the next cohort initiates accrual. Barring DLT, sequential dose escalation of BTX-A51 is planned with up to a total of 6 dose levels; on the basis of these an MTD will be identified. The MTD is defined as the highest dose level with a subject incidence of DLTs of 0 or 1 out of 6 during the first 28 days of study drug dosing. A minimum of 6 subjects needs to be treated at a dose level before this dose level can be deemed as the MTD. Phase 1b (Monotherapy Dose Ranging Phase): Dose expansion may begin when the RP2D has been determined. Up to 40 additional subjects at each of the 2 dose levels will be enrolled to evaluate safety and preliminary efficacy of BTX-A51 in subjects with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-), GATA3 mutant (mt) and wild-type (wt) metastatic breast cancer (mBC). Dosing in this phase of the study consists of the first cycle of therapy (i.e., 28 days). Phase 1c (Combination Safety Phase): The Phase 1c portion will evaluate the safety and tolerability of orally administered BTX-A51 at two dose levels combined with fulvestrant. The first combo cohort may be initiated after DEC review of the 6 subject lead-in phase of the high dose monotherapy cohort in Phase 1b. Dose escalation will proceed according to a 3+3 design. Each cycle will consist of 28 days (4 weeks), and the DLT observation period will be the first cycle (i.e., 28 days after initiation of dosing).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
112
One 28 day cycle of treatment will consist of 4 weeks of treatment with a weekly dosing schedule of up to 5 days per weekf.
Florida Cancer Specialists
Lake Mary, Florida, United States
RECRUITINGFlorida Cancer Specialists
Sarasota, Florida, United States
RECRUITINGThe Linder Research Center at The Christ Hospital
Cincinnati, Ohio, United States
COMPLETEDSCRI Oncology Partners
Nashville, Tennessee, United States
RECRUITINGTennessee Oncology, PLLC
Nashville, Tennessee, United States
COMPLETEDThe University of Texas MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGIncidence of adverse events after BTX-A51 administration alone and in combination with fulvestrant
To examine the incidence of clinical and laboratory adverse events after multiple doses of BTX-A51 alone and in combination with fulvestrant.
Time frame: From first dose of BTX-A51 through 30 days after the last BTX-A51 alone and in combination with fulvestrant treatment (subjects will be offered continued access to study BTX-A51 until disease progression or unacceptable toxicity)
Defining the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of BTX-A51alone and in combination with fulvestrant
To assess number of patients experiencing dose-limiting toxicities (DLTs)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Objective response rate (ORR)
To evaluate the objective response rate (ORR) as determined by the specific disease response criteria
Time frame: Up to 2 years after the last treatment or upon death.
Duration of response (DoR)
To evaluate the duration of response (DoR), defined as time from the date of first documentation of response to the date of the first documentation of progressive disease (PD), or death due to any cause
Time frame: Up to 2 years after the last treatment or upon death.
Progression free survival (PFS)
To examine the the progression free survival (PFS), defined as time from the date of first dose of study treatment to the first date of documentation of PD, or death due to any cause
Time frame: Up to 2 years after the last treatment or upon death.
Overall survival (OS)
To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause
Time frame: Up to 2 years after the last treatment or upon death.
Peak Plasma Concentration of BTX-A51
To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of BTX-A51
Time frame: PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, 8, and 24 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Area under the plasma concentration of BTX-A51
To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of BTX-A51
Time frame: PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, 8, and 24 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Half-life of BTX-A51
To evaluate the half-life of BTX-A51 after single and repeated oral, once daily doses of BTX-A51
Time frame: PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, 8, and 24 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
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