Metformin + Digoxin + Simvastatin for Pancreatic Cancer

Overseen By Danielle Mockensturm

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Danae Hamouda

Must not be taking: Metformin, Simvastatin, Digoxin

Disqualifiers: Other malignancy, Brain metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of 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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had anti-cancer chemotherapy, biologic therapy, or immunotherapy within 3 weeks, or radiation therapy within 2 weeks of starting the trial.

What makes the drug combination of Metformin, Digoxin, and Simvastatin unique for treating pancreatic cancer?

This drug combination is unique because it combines Metformin, known for its use in diabetes, and Simvastatin, a cholesterol-lowering drug, both of which have shown potential anticancer effects, with Digoxin, which affects cellular pathways involved in cancer. Simvastatin has been found to slow tumor growth in pancreatic cancer models, and the combination of Metformin and statins may have synergistic effects, potentially offering a novel approach to treatment. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Metformin, Digoxin, and Simvastatin for treating pancreatic cancer?

Research suggests that simvastatin, one of the drugs in the combination, may slow tumor growth in pancreatic cancer models. Additionally, a study found that statin use, which includes simvastatin, was associated with improved survival in elderly pancreatic cancer patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Danae Hamouda, MD

Principal Investigator

University of Toledo

Are You a Good Fit for This Trial?

Adults (≥18 years) with advanced solid tumors, including pancreatic cancer, that are not responding to standard treatments can join. They must have a performance status indicating they're still relatively active and able to care for themselves. Women who can bear children need a negative pregnancy test. Participants should be recovered from previous therapies' side effects and have normal organ/marrow function.

Inclusion Criteria

My blood tests show normal organ function and healthy blood cell counts.

Ability to understand and the willingness to sign a written informed protocol specific consent

I have recovered from side effects of previous treatments, except for some nerve issues.

Exclusion Criteria

I am pregnant or nursing.

I have a heart condition like Wolff-Parkinson-White Syndrome or a history of serious heart issues.

I had another cancer but was treated successfully over 3 years ago, except for certain skin, bladder, or in situ cancers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Treatment

Participants receive C3 (Metformin, Simvastatin, and Digoxin) in a dose escalation format over 28-day cycles

28 days per cycle, multiple cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Extension

Participants may continue treatment at the maximum tolerated dose in an expansion cohort

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Digoxin
• Metformin
• Simvastatin

Trial Overview This trial is testing the combination of Metformin, Digoxin, and Simvastatin in patients with advanced solid tumors including pancreatic cancer. It's an open-label study where everyone gets the same treatment but at different doses to find out how much can be given safely.

How Is the Trial Designed?

Group I: Dose Escalation Experimental Treatment 3 Interventions

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 once daily.

Digoxin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Lanoxin for:

• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
• Congestive heart failure

Approved in United States as Lanoxin for:

• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
• Congestive heart failure

Approved in Canada as Lanoxin for:

• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
• Congestive heart failure

Approved in Japan as Lanoxin for:

• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
• Congestive heart failure

Who Is Running the Clinical Trial?

Danae Hamouda

Lead Sponsor

Trials

1

Recruited

20+

Danae Hamouda, MD

Lead Sponsor

Trials

1

Recruited

20+

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Digoxin use is associated with pancreatic cancer risk but does not affect survival. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Simvastatin Attenuated Tumor Growth in Different Pancreatic Tumor Animal Models. [2023]

3. Ireland pubmed.ncbi.nlm.nih.gov

Repurposing metformin, simvastatin and digoxin as a combination for targeted therapy for pancreatic ductal adenocarcinoma. [2022]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effect of Metformin and Statin Use on Survival in Pancreatic Cancer Patients: a Systematic Literature Review and Meta-analysis. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Differential and Joint Effects of Metformin and Statins on Overall Survival of Elderly Patients with Pancreatic Adenocarcinoma: A Large Population-Based Study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Pitavastatin and metformin synergistically activate apoptosis and autophagy in pancreatic cancer cells. [2021]