Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial)
- Registration Number
- NCT03834220
- Lead Sponsor
- Debiopharm International SA
- Brief Summary
The primary objective of this study is to assess the efficacy of Debio 1347 in terms of objective response rate (ORR) in participants with solid tumors harboring fibroblast growth factor receptor (FGFR)1-3 gene fusion/rearrangement.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 63
- Cytologically or histologically confirmed advanced solid tumor
- Radiographic progression on prior systemic therapy; prior localized therapy (i.e., radiation, ablation, embolization) is allowed provided radiographic progression out-of-field or in the treatment, field is shown
- Locally-advanced (unresectable) or metastatic disease harboring an FGFR1-3 gene fusion/rearrangement potentially leading to a functional FGFR aberrant protein, identified through local and/or central molecular assay
- History of hypersensitivity to any of the excipients in the Debio 1347 formulation
- History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes, lung nodules and asymptomatic vascular or cartilage/tendon calcifications
- Administration of any investigational agent within 2 weeks prior to initial dosing with Debio 1347 (3 weeks for immune checkpoint inhibitors)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2: Debio 1347 (Urothelial Cancer) Debio 1347 Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks). Cohort 1: Debio 1347 (Biliary Tract Cancer) Debio 1347 Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks). Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) Debio 1347 Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria Up to disease progression or end of study (up to 1 year and 9 months) ORR was defined as the percentage of participants with a best overall response (BOR) of partial or complete response (PR or CR). BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) as Centrally Measured by Independent Review Committee (IRC) Up to disease progression or end of study (up to 2 years and 9 months) DOR was defined as the time from the date of the initial PR or CR to date of the first documented progression or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs) From first dose of study drug up to 30 days post last dose (Up to 2 years and 9 months) An AE is any untoward medical occurrence in a participant or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE that either starts or worsens in severity on or after the first administration of the study drug and within 30 days of the last administration of the study drug. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days) Geometric mean and geometric percent CV summary was estimated based on log-linear model.
Correlation of Debio 1347 Plasma Concentration (C) and QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Pre-dose on Days 14 and 28, and 1, 3, 7 hours post-dose on Day 28 of Cycle 1; pre-dose on Days 14 and 28, and 3 hours post-dose on Day 28 of Cycle 2 (each cycle length = 28 days) Progression-Free Survival (PFS) as Centrally Measured by Independent Review Committee (IRC) From the start of the study up to disease progression or death (up to 2 years and 9 months) PFS was defined as the time from the start date of treatment to date of the first documented progression or death due to any cause.
Disease Control Rate (DCR) as Centrally Measured by Independent Review Committee (IRC) Up to disease progression or end of study (up to 2 years and 9 months) DCR was defined as the percentage of participants with a BOR of confirmed CR, confirmed PR or stable disease (SD) ≥6 weeks. BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Overall Survival (OS) Until death or loss to follow-up or end of study (up to 2 years and 9 months) OS was defined as the time from the start date of treatment to date of death due to any cause. Participants with no documented death were censored at the last date known to be alive.
Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days) Geometric mean and geometric percent CV summary was estimated based on log-linear model.
Trial Locations
- Locations (104)
Ironwood Cancer & Research Centers - Scottsdale
🇺🇸Scottsdale, Arizona, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
🇺🇸Tampa, Florida, United States
James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Tulane University Cancer Center
🇺🇸New Orleans, Louisiana, United States
The John Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
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