A Phase 3, Multicenter, Randomized, Open-label, Study Evaluating the Efficacy and Safety of Nanvuranlat in Patients With Previously Treated Advanced Biliary Tract Cancer
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- J-Pharma Co., Ltd.
- Enrollment
- 480
- Locations
- 20
- Primary Endpoint
- Part A: Preliminary Overall Survival (OS)
Overview
Brief Summary
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.
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •\- Individuals are eligible to be included in the study only if all of the following criteria apply:
- •At least 18 years of age inclusive at the time of signing the informed consent.
- •Provides informed written consent according to local laws or regulations.
- •Able and willing to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including peripheral blood and urine sampling during the study.
- •Willing to participate in LAT1 testing and NAT2 and transporter genotyping. Note: For LAT1 testing, if the participant does not have archival tissue and a fresh biopsy is not in the best interest of the participant, they will still be eligible for the trial.
- •Cancer must be metastatic, locally advanced and unresectable, or not amenable to treatment with local therapies that could offer a reasonable likelihood of clinical benefit.
- •Histologic or cytologic diagnosis of BTC.
- •Has BTC that is classified as either an IHC, EHC, or GBC based on surgical, clinical, or laparoscopic findings and/or radiological imaging (eg, CT, MRI).
- •Has received 1 prior appropriate platinum (cisplatin, carboplatin, or oxaliplatin)-based therapy for advanced disease (locally advanced or metastatic) with or without a mAb targeting PD-1 or PD-L
- •Disease progression during or within 6 months of neoadjuvant or adjuvant treatment with a platinum-containing regimen will count as having received 1 prior regimen.
Exclusion Criteria
- •Individuals will be excluded from study participation if they meet any of the following criteria:
- •Received systemic therapy or an investigational agent before washing out, as follows:
- •\< 2 weeks prior to Cycle 1 Day 1 for systemic non-immune-based therapy
- •\< 3 weeks prior to Cycle 1 Day 1 for immune-based therapy
- •≤ 5 half-lives or 3 weeks (whichever is longer) prior to Cycle 1 Day 1 for an investigational agent
- •Received radiotherapy to metastatic sites within 2 weeks of Cycle 1 Day
- •Patients must have recovered from all radiation-related toxicities and not require corticosteroids. A 1 week washout is permitted for palliative radiation with a limited port ≤ 2 weeks of radiotherapy to non-CNS disease.
- •Underwent hepatic radiation, chemoembolization, or radiofrequency ablation \< 4 weeks prior to Cycle 1 Day
- •Underwent major surgery \< 3 weeks before Screening and has not recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
- •Known active CNS metastases and/or carcinomatous meningitis. Those with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of PD for at least 4 weeks by repeat imaging), clinically stable, and without requirement of corticosteroid treatment for at least 14 days prior to first dose of study intervention. For those with a history of CNS involvement, repeat imaging should be performed during study screening. However, CNS imaging is not required prior to study entry unless there is clinical suspicion of CNS involvement.
Arms & Interventions
Nanvuranlat 50mg
Nanvuranlat 50mg administered via a 90-minute intravenous infusion once daily for 5 consecutive days, followed by 9 days off treatment
Intervention: Nanvuranlat (Drug)
Navuranlat 375mg
Nanvuranlat 375mg administered via a 46-hour continuous intravenous infusion once every 14 days
Intervention: Nanvuranlat (Drug)
Physicians Best Choice (PBC)
- FOLFOX regimen (Leucovorin, 5-Flurouracil and Oxaliplatin) administered on Day 1 of each 14 day cycle, or
- FOLFIRI regimen (Leucovorin, 5-Flurouracil and Irinotecan) administered once during 14 day cycle, or
- Best Supportive Care (BSC) including symptomatic therapeutics, palliative radiation for pre-existing metastases and transfusion of blood products administered at discretion of Investigator.
Intervention: Physician's Best Choice (Other)
Navuranlat 75mg
Nanvuranlat 75mg administered via a 90-minute intravenous infusion once daily for 5 consecutive days, followed by 9 days off treatment
Intervention: Nanvuranlat (Drug)
Outcomes
Primary Outcomes
Part A: Preliminary Overall Survival (OS)
Time Frame: From date of first dose of study intervention until death [Approx. 24 months].
OS is defined as the time from the date of Cycle 1 Day 1 to the date of death from any cause.
Part B: Overall Survival
Time Frame: From date of first dose of study intervention until death [Approx. 36 months]
OS is defined as the time from the date of Cycle 1 Day 1 to the date of death from any cause.
Secondary Outcomes
- Part B: Progression Free Survival(From first dose of study intervention until disease progression or death (which ever occurs first) [Approx. 36 months].)
- Part B: Objective Response Rate(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)(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(From first dose of study intervention and up to first 8 weeks of treatment [Approx. 36 months].)
- Part B: Dose Reductions, Interruptions and Discontinuations(From first dose of study intervention through last dose of study drug intervention [Approx. 36 months].)
- Part B: Electrocardiograms(From first dose of study intervention through last dose of study drug intervention [Approx. 36 months].)