This study aims to test the hypothesis that combining serabelisib, a PI3K alpha isoform inhibitor, with an SGLT2 inhibitor, canagliflozin will improve efficacy in the treatment of patients with advanced solid tumors.
This study aims to test the hypothesis that controlling the glucose/insulin feedback will enhance the efficacy of PI3K inhibition in treating solid tumors. The treatment consists of serabelisib, a PI3K alpha isoform (PI3Kα) inhibitor, combined with the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin. The study will assess the safety and efficacy of the combination in adult patients with advanced solid tumors harboring mutations that may be dependent on PI3Kα activity: PIK3CA mutations and KRAS mutations.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Subjects will be dosed with Serabelisib on 3 consecutive days a week in a 28 day cycle until tumor progression. in combination with Canagliflozin 300mg, both are oral medications
All subjects will be dosed with 300 mg canagliflozin in combination with serabelisib
Rate of Adverse Events
Safety of serabelisib in combination with canagliflozin as evaluated by incidence of drug-related adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities.
Time frame: 30 days after last dose
Rate of Laboratory Abnormalities
Safety of serabelisib in combination with canagliflozin as evaluated by incidence of clinical laboratory abnormalities
Time frame: 30 days after last dose
Dose confirmation
To confirm the appropriate dose of serabelisib to be coadministered with canagliflozin
Time frame: 6 months
Tumor Assessments by RESIST
To assess efficacy of serabelisib in combination with canagliflozin in patients with solid tumors with PIK3CA or KRAS mutations
Time frame: 2 years
Cmax Pharmacokinetic assessment
Maximum observed plasma concentration (Cmax) of serabelisib
Time frame: Day 1 and 8 of Cycle 1: pre-dose and then post-dose at 1.5 hours, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours
Tmax Pharmacokinetic assessment
Time of maximum observed plasma concentration (Tmax) of serabelisib
Time frame: Day 1 and 8 of Cycle 1: pre-dose and then post-dose at 1.5 hours, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours
AUC Pharmacokinetic assessment
Area under the plasma concentration time curve in the dosing interval AUC of serabelisib
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Time frame: Day 1 and 8 of Cycle 1: pre-dose and then post-dose at 1.5 hours, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours