Phase IB Metformin, Digoxin, Simvastatin in Solid Tumors
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|ClinicalTrials.gov Identifier: NCT03889795|
Recruitment Status : Recruiting
First Posted : March 26, 2019
Last Update Posted : October 8, 2020
|Condition or disease||Intervention/treatment||Phase|
|Advanced Pancreatic Cancer Advanced Solid Tumor||Drug: Metformin Drug: Simvastatin Drug: Digoxin||Phase 1|
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 (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||3 Subjects per Cohort + 3 additional subjects in Expansion Cohort.|
|Masking:||None (Open Label)|
|Official Title:||Phase IB Trial of Metformin, Digoxin, Simvastatin in Subjects With Advanced Pancreatic Cancer and Other Advanced Solid Tumors|
|Actual Study Start Date :||June 5, 2019|
|Estimated Primary Completion Date :||December 30, 2021|
|Estimated Study Completion Date :||December 30, 2022|
Experimental: Dose Escalation
C3 (Metformin, Simvastatin and Digoxin) will be dosed each day of a 28 calendar day cycle. The starting dose level will be increased with each cohort. There are 3 cohorts. Upon reaching maximum tolerated dose, an expansion cohort will be opened. Cohort 1 - Metformin 850mg po/day, Simvastatin 5mg po/day, Digoxin 0.0625 mg po/day. Cohort 2 - Metformin 850 mg po/day for two weeks and 1,700 mg po/day for next two weeks, Simvastatin 20 mg po/day, Digoxin 0.25 mg po/day. Cohort 3 - Metformin 850 mg po/day for two weeks and 1,700 mg po/day for next two weeks, Simvastatin 40 mg po/day, Digoxin 0.25 mg po/day for two weeks, 0.375 mg po/day for the next two weeks for cycle 1. Subjects will receive 0.50 mg po/day in Cohort 3, Cycle 2 and beyond. Metformin to be taken at Breakfast and Dinner time (as applicable), Simvastatin at Bed time and Digoxin in the Morning.
Metformin oral pill will be taken daily at breakfast (cohort 1) and breakfast and dinner (cohort 2 and 3).
Other Name: Glucophage
Simvastatin oral pill will be taken daily in the evening.
Other Name: Zocor
Digoxin oral pill will be taken daily in the morning.
Other Name: Digitalis
- Maximum Tolerated Dose and/or Recommended Dose within the tested C3 dose range [ Time Frame: Up to one year ]Occurrence of any ≥ Grade 3 toxicity encountered within the four weeks following the administration of C3, regardless of attribution
- Safety and Tolerability: Occurrence of treatment - emergent adverse events (TEAEs) and other abnormalities [ Time Frame: Up to 2 years ]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
- Efficacy (Disease Response) [ Time Frame: Up to 2 years ]Response and progression evaluated using Response Evaluation criteria in solid tumors
- Assess BIRC5 levels of expression in tumor tissue [ Time Frame: RNA and protein levels of expression at baseline and at 2 months after C3 treatment ]Blood samples for pharmacokinetic analysis of C3 will be collected at designated time points.
- Assess molecular changes induced by C3 administration in the blood for biomarker sensitivity/resistance assessment [ Time Frame: Baseline and at 2 months ]Molecular signal tumor blood (plasma) and microenvironment protein expression patterns via quantitative mass spectrometry.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03889795
|Contact: Stephanie Smiddy, RN||419-383-4000 ext firstname.lastname@example.org|
|United States, Ohio|
|University of Toledo, Eleanor N. Dana Cancer Center||Recruiting|
|Toledo, Ohio, United States, 43614|
|Contact: Stephanie Smiddy, RN, BSN 419-383-4000 ext 6962 email@example.com|
|Principal Investigator: John J Nemunaitis, MD|
|Principal Investigator:||John J. Nemunaitis, MD||The University of Toledo|