This study is designed to 1) select a dose regimen for continued development and 2) evaluate nanvuranlat versus Physicians Best Choice (PBC) (FOLFOX, FOLFIRI, or Best Supportive Care (BSC)) in participants aged 18 years and over with BTC. Participants enrolling in Part A the trial will be randomly assigned to receive 1 of 3 nanvuranlat dose regimens or PBC. In Part B, participants will be randomly assigned to receive nanvuranlat or PBC. Participants will receive treatment every 2 weeks for as long as they do not experience safety issues, or their cancer gets worse, and the study doctor feels they should stop treatment. Health measurements including physical examinations, vital signs, ECGs, and safety laboratory tests will be performed to monitor safety, and tumor imaging will be performed to monitor cancer response to treatment. Other exploratory makers will be measured to better understand how nanvuranlat works.
This is a Phase 3, multicenter, randomized, open-label, 2-part study designed to select a dose regimen for continued development (Part A) and evaluate the efficacy and safety of nanvuranlat versus PBC (Part B) for the treatment of patients with advanced (locally advanced or metastatic) BTC who have previously received 1 prior standard therapy for advanced BTC plus appropriate therapies targeting druggable molecular mutations/aberrations. Randomization will be stratified by disease subtypes: IHC, EHC, and GBC. Part A (Dose Regimen Selection) - Three nanvuranlat dose regimens will be evaluated in Part A. Cohorts 1 and 2 will receive 50 or 75 mg of nanvuranlat via a 90-minute infusion, once daily for 5 days, followed by 9 days treatment free (Nanvuranlat-5/9). Cohort 3 will receive 375 mg of nanvuranlat via a 46-hour infusion once every 14 days (Nanvuranlat-46). Participants will be randomized 1:1:1:1 to 4 cohorts. Each treatment cycle will be 14 days and study intervention will be administered beginning on Day 1 during each treatment cycle, except for those participants receiving BSC who will receive care at the discretion of the Investigator. Part B (Efficacy Evaluation) - Participants will be randomized 1:1 to either nanvuranlat (dose regimen selected in Part A) or PBC (FOLFOX, FOLFIRI, or BSC). Each treatment cycle will be 14 days and study intervention will be administered beginning on Day 1 during each treatment cycle, except for those participants receiving BSC who will receive care at the discretion of the Investigator.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
480
Nanvuranlat, IV administration
1. FOLFOX regimen (Leucovorin, 5-Flurouracil and Oxaliplatin) administered on Day 1 of each 14 day cycle, or 2. FOLFIRI regimen (Leucovorin, 5-Flurouracil and Irinotecan) administered once during 14 day cycle, or 3. Best Supportive Care (BSC) including symptomatic therapeutics, palliative radiation for pre-existing metastases and transfusion of blood products administered at discretion of Investigator.
Banner MD Anderson Cancer Center (Site 106)
Gilbert, Arizona, United States
NOT_YET_RECRUITINGCity of Hope (Site 107)
Duarte, California, United States
NOT_YET_RECRUITINGUniversity of California at Irvine (Site 101)
Orange, California, United States
NOT_YET_RECRUITINGUCLA Medical Center (Site 117)
Santa Monica, California, United States
NOT_YET_RECRUITINGNorton Cancer Institute (Site 115)
Louisville, Kentucky, United States
NOT_YET_RECRUITINGOchsner Medical Center (Site 120)
New Orleans, Louisiana, United States
NOT_YET_RECRUITINGHenry Ford Cancer Center (Site 113)
Detroit, Michigan, United States
NOT_YET_RECRUITINGKarmanos Cancer Center (Site 109)
Detroit, Michigan, United States
NOT_YET_RECRUITINGMasonic Cancer Center, University of Minnesota (Site 116)
Minneapolis, Minnesota, United States
NOT_YET_RECRUITINGRutgers Cancer Institute of New Jersey (Site 103)
New Brunswick, New Jersey, United States
RECRUITING...and 8 more locations
Part A: Preliminary Overall Survival (OS)
OS is defined as the time from the date of Cycle 1 Day 1 to the date of death from any cause.
Time frame: From date of first dose of study intervention until death [Approx. 24 months].
Part B: Overall Survival
OS is defined as the time from the date of Cycle 1 Day 1 to the date of death from any cause.
Time frame: From date of first dose of study intervention until death [Approx. 36 months]
Part B: Progression Free Survival
PFS is defined as the time from the date of Cycle 1 Day 1 to the date of objectively determined progression of disease per the Investigators using RECIST version 1.1 or death from any cause, whichever occurs first.
Time frame: From first dose of study intervention until disease progression or death (which ever occurs first) [Approx. 36 months].
Part B: Objective Response Rate
ORR, defined as the proportion of patients achieving a best response of CR or PR per the Investigators using RECIST version 1.1.
Time frame: From first dose of study intervention until disease progression or death (which ever occurs first) [Approx. 36 months].
Part B: Incidence of treatment-emergent adverse events (TEAEs)
Incidence of TEAEs, including serious adverse events (SAEs)
Time frame: From first dose of study intervention and up to 30 days after last dose of study intervention [Approx. 36 months].
Part B: Relative Dose Intensity
Relative dose intensity is defined as the ratio of completed infusions to the total planned infusions of the study drug during the first 8 weeks of treatment.
Time frame: From first dose of study intervention and up to first 8 weeks of treatment [Approx. 36 months].
Part B: Dose Reductions, Interruptions and Discontinuations
Incidence of dose reductions, Interruptions and Discontinuations
Time frame: From first dose of study intervention through last dose of study drug intervention [Approx. 36 months].
Part B: Electrocardiograms
Proportion of patients with treatment-emergent clinically significant ECG abnormalities
Time frame: From first dose of study intervention through last dose of study drug intervention [Approx. 36 months].
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