This is a single-center trial in subjects with pancreatic cancer and other advanced solid tumors. It is an open-label, single arm dose escalation Phase IB trial with subjects accrued in a 3 subject dose escalation cohort. Subjects with treated advanced solid tumors, and showing disease progression on established standard therapy, will be enrolled in this trial.
This is a single-center trial in subjects with pancreatic cancer and other advanced solid tumors. It is an open-label, single arm dose escalation Phase IB trial with subjects accrued in a 3 subject dose escalation cohort. Subjects with treated advanced solid tumors, and showing disease progression on established standard therapy, will be enrolled in this trial. C3 (Simvastatin + Digoxin + Metformin) will be given as three oral pills within recommended package insert safe levels. Subjects will be accrued in 3-subject dose escalation cohorts. 3 additional subjects will be treated at the presumptive maximum effective cohort dose/schedule for a total of 6 subjects at maximum effective level.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Metformin oral pill will be taken daily at breakfast (cohort 1) and breakfast and dinner (cohort 2 and 3).
Simvastatin oral pill will be taken daily in the evening.
Digoxin oral pill will be taken once daily.
University of Toledo, Eleanor N. Dana Cancer Center
Toledo, Ohio, United States
Maximum Tolerated Dose and/or Recommended Dose within the tested C3 dose range
Occurrence of any ≥ Grade 3 toxicity encountered within the four weeks following the administration of C3, regardless of attribution
Time frame: Up to one year
Safety and Tolerability: Occurrence of treatment - emergent adverse events (TEAEs) and other abnormalities
Occurrence of treatment - emergent adverse events (TEAEs) and occurrence of abnormalities in laboratory test values, markedly abnormal vital sign measurements, and clinically significant abnormal electrocardiograms (ECGs), including conduction abnormalities and changes in QT interval
Time frame: Up to 2 years
Efficacy (Disease Response)
Response and progression evaluated using Response Evaluation criteria in solid tumors
Time frame: Up to 2 years
Assess BIRC5 levels of expression in tumor tissue
Blood samples for pharmacokinetic analysis of C3 will be collected at designated time points.
Time frame: RNA and protein levels of expression at baseline and at 2 months after C3 treatment
Assess molecular changes induced by C3 administration in the blood for biomarker sensitivity/resistance assessment
Molecular signal tumor blood (plasma) and microenvironment protein expression patterns via quantitative mass spectrometry.
Time frame: Baseline and at 2 months
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