A phase I/II, open-label, study to determine the safety and preliminary efficacy of orellanine in patients with metastatic clear-cell or papillary renal carcinoma who have failed standard-of-care therapy. All participants must have end-stage kidney disease and be receiving stable chronic hemodialysis.
This is an open, non-controlled, phase I/II study evaluating the safety, tolerability, and anti-tumor efficacy of orellanine treatment in patients with metastatic clear-cell or papillary renal carcinoma. The study will include up to 75 patients and is conducted in 3 parts. The study will consist of 3 parts: Part A - an intra-patient dose escalation part, followed by a dose exposure (Part B), followed by a dose expansion (Part C). Part A, which is now closed, used an intra patient dose escalation design to evaluate safety across multiple dose levels. The study is currently in Part B, an exposure based dose escalation phase. Patients may be enrolled into either a 24 hour or a 72 hour exposure cohort. Exposure duration is defined by the timing of hemodialysis, as elimination of orellanine occurs primarily through dialysis initiated after infusion. The starting dose for Part B is 0.38 mg/kg, and the total dose per treatment cycle is limited to 2.5 mg/kg, including any replacement doses. A minimum of three patients will be enrolled in each cohort, and escalation to longer exposure durations occurs only after safety evaluation. Part C is a planned dose expansion phase to further characterize safety and explore preliminary antitumor activity at the selected dose and exposure level.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
75
Orellanine administered intravenously
Stanford
Palo Alto, California, United States
RECRUITINGWashington University in St. Louis
St Louis, Missouri, United States
RECRUITINGUniversity of Texas - MD Anderson Cancer Center
Houston, Texas, United States
Adverse events and laboratory abnormalities as graded by NCI CTCAE v5.0.
Time frame: Through study completion, approximately 1 year
Changes in arterial blood pressure measurements
Time frame: Through study completion, approximately 1 year
Changes in pulse rate measurements
Time frame: Through study completion, approximately 1 year
Changes in respiratory rate measurements
Time frame: Through study completion, approximately 1 year
Changes in temperature measurements
Time frame: Through study completion, approximately 1 year
Changes in physical examination findings
Time frame: Through study completion, approximately 1 year
Maximum tolerable dose of orellanine
Time frame: Through study completion, approximately 1 year
Efficacy of orellanine based on time to tumor response
Time frame: Through study completion, approximately 1 year.
Efficacy of orellanine based on best overall response
Time frame: Through study completion, approximately 1 year.
Area under the curve extrapolated to infinity
Time frame: Through study completion, approximately 1 year.
Terminal half-life
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START Lisbon - Hospital de Santa Maria Av
Lisbon, Portugal
RECRUITINGKarolinska University Hospital
Stockholm, Sweden
RECRUITINGTime frame: Through study completion, approximately 1 year.
Partial area under the curve
Time frame: Through study completion, approximately 1 year.
Dose proportionality
Time frame: Through study completion, approximately 1 year.
Time to maximum plasma concentration
Time frame: Through study completion, approximately 1 year.
Maximum plasma concentration
Time frame: Through study completion, approximately 1 year.
Total body clearance
Time frame: Through study completion, approximately 1 year.
Volume of distribution
Time frame: Through study completion, approximately 1 year.