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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose for a combination of three drugs—Metformin, Digoxin (a heart medication), and Simvastatin—to treat pancreatic cancer and other advanced solid tumors. The goal is to assess whether these drugs can benefit individuals whose cancer has not responded to standard treatments. Ideal participants have a confirmed solid tumor, have tried other treatments without success, and are willing to undergo a biopsy (a procedure to take a small sample of tissue). As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using metformin, simvastatin, and digoxin together might benefit people with pancreatic cancer. Studies have found that simvastatin can slow tumor growth. Additionally, taking metformin and statins (like simvastatin) together may improve survival rates for these patients.

Regarding safety, these medicines are usually well-tolerated when used separately for other health issues. Metformin is commonly used for diabetes, simvastatin helps control cholesterol, and digoxin is used for heart problems. However, the safety of using all three together remains under investigation. This trial is in its early stages and primarily focuses on finding the safest dose that people can handle without excessive side effects.

Prospective participants can be assured that researchers are carefully adjusting doses to ensure both effectiveness and safety. While side effects are possible, the aim is to minimize them while exploring the potential benefits of this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Metformin, Digoxin, and Simvastatin for pancreatic cancer because it offers a novel approach by repurposing existing drugs with well-known safety profiles. Unlike standard treatments which often focus on chemotherapy, this combination targets cancer cells' metabolism and reduces their ability to grow and spread. Digoxin, typically used for heart conditions, disrupts cellular ion balance, Metformin enhances energy regulation, and Simvastatin inhibits cholesterol production in cancer cells. This unique combination might offer a more targeted and potentially less toxic alternative to traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

This trial will evaluate the combination of Metformin, Simvastatin, and Digoxin for treating pancreatic cancer. Research has shown that Simvastatin can slow tumor growth in pancreatic cancer. When combined with Metformin, commonly used for diabetes, the effect might be even stronger. Metformin not only controls blood sugar but also shows promise in cancer treatment by potentially affecting cancer cell energy use. Digoxin, typically used for heart issues, might help fight cancer by interfering with cancer cell growth and survival. Although more research is needed, early results suggest that using these drugs together could offer new hope for treating pancreatic cancer. ^{1 2 3 6 7}

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8766172/

Repurposing Metformin, Simvastatin and Digoxin as a ... Patients with pancreatic adenocarcinoma (PDAC) have a 5-year survival rate of 8%, the lowest of any cancer in the United States.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03889795

Phase IB Metformin, Digoxin, Simvastatin in Solid Tumors 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0304383520304134

Repurposing metformin, simvastatin and digoxin as a ... Patients with pancreatic adenocarcinoma (PDAC) have a 5-year survival rate of 8%, the lowest of any cancer in the United States.

4. withpower.com withpower.com/trial/phase-1-pancreatic-neoplasms-5-2019-ab2d1

Metformin + Digoxin + Simvastatin for Pancreatic Cancer Simvastatin has been found to slow tumor growth in pancreatic cancer models, and the combination of Metformin and statins may have synergistic effects, ...

5. ctv.veeva.com ctv.veeva.com/study/phase-ib-metformin-digoxin-simvastatin-in-solid-tumors

Phase IB Metformin, Digoxin, Simvastatin in Solid Tumors This is a single-center trial in subjects with pancreatic cancer and other advanced solid tumors. It is an open-label, single arm dose ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06030622

Study Details | NCT06030622 | Phase 2A Pilot C3 Trial of ... Recent studies have shown that the use of metformin and simvastatin in 15,099 patients with pancreatic cancer significantly improved their survival.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5638687/

Effect of Metformin and Statin Use on Survival in Pancreatic ... Our findings suggest that the improved survival time of pancreatic cancer patients are associated with statin or metformin use.