This is a phase 1, First-In-Human, open label study, trialing a new PARP (poly-ADP ribose polymerase) inhibitor medication IMP4297 in participants with advanced solid tumour.
This is a phase 1, First-In-Human, open label study, trialing a new PARP inhibitor medication IMP4297 in participants with advanced solid tumour. Six different dosage cohorts 2mg, 6mg, 10mg, 20mg, 30mg and 40mg will be used to establish the maximum tolerated dosage. First participant in each dosing cohort will be administered one dose of IMP4297 capsule, followed by a wash out period of at least 5 half-lives or 7 days. Safety information such as pathology result or adverse events experienced will be collected following first dosing. This will be reviewed by the a safety review committee that is made up of the Principal Investigator, Medical Monitor, the study Sponsor and a representative from the Clinical Research Organisation, which will collectively determine if it is safe to proceed to continue with the next scheduled dosing cohort. Participant will proceed with repeat once daily dose at the same dose level for 3 weeks. Each repeat dose treatment cycle will be composed of 3 weeks (Day 1 to Day 21). IMP4297 will be administered by participants at home. Participants will be instructed to bring unused IMP4297 capsules with them to each visit for trial staff to review and confirm amount of IMP4297capsules taken since the last visit. The administration of the IMP4297 capsules will be recorded. Study drug compliance will be assessed using these records in conjunction with a count of unused IMP4297 capsules. Participants who are benefiting from IMP4297 may have the possibility of treatment beyond 1 year at the investigator's discretion. Participants who experience disease progression or unacceptable side effects, are not compliant with study protocol or in the opinion of the investigator will have IMP4297 administration discontinued and study participation will be terminated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
39
The dose levels will be escalated following a modified 3+3 dose escalation scheme.
Blacktown Hospital
Blacktown, New South Wales, Australia
St George Private Hospital
Kogarah, New South Wales, Australia
Nucleus Network
Melbourne, Victoria, Australia
The AEs (adverse event) of single and multiple doses of IMP4297 administered to participants with advanced solid tumors.
Evaluate the TEAE (treatment-emergent adverse event) of IMP4297
Time frame: Each visit after IMP4297 administrated (through study completion, an average of 10 months)
The maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLTs) of IMP4297.
Evaluate DLT and determine the MTD
Time frame: Within 28 days after IMP4297 administrated
Area Under Curve [AUClast, AUCINF and AUCtau]
Time frame: Within 7 days after firstly single dose administrated
Area Under Curve [AUClast, AUCINF and AUCtau]
Time frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle)
Maximum plasma concentration (Cmax)
Time frame: Within 7 days after firstly single dose administrated
Maximum plasma concentration (Cmax)
Time frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle)
Time at which Cmax occurred (Tmax)
Time frame: Within 7 days after firstly single dose administrated
Time at which Cmax occurred (Tmax)
Time frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle)
Trough Concentrations (Ctrough)
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Time frame: Within 7 days after firstly single dose administrated
Trough Concentrations (Ctrough)
Time frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle)
Clearance (CL/F)
Time frame: Within 7 days after firstly single dose administrated
Clearance (CL/F)
Time frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle)
Volume of distribution (Vd/F)
Time frame: Within 7 days after firstly single dose administrated
Volume of distribution (Vd/F)
Time frame: Within 16 days after first dose administrated in multiple dose cycle 1 (total 21 days in one cycle)