Cholesterol-Lowering Drug + Chemotherapy for Pancreatic Cancer

Not currently recruiting at 2 trial locations

Overseen By Anne Gangloff, MD PhD FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: CHU de Quebec-Universite Laval

Must be taking: Cholesterol-lowering drugs

Must not be taking: Statins, PCSK9 inhibitors

Disqualifiers: Operable cancer, Other malignancy, Myalgia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether lowering cholesterol can enhance the effectiveness of chemotherapy in fighting pancreatic cancer. It combines three cholesterol-lowering drugs with standard chemotherapy to determine if this approach slows or stops cancer growth. The trial seeks participants recently diagnosed with locally advanced or metastatic pancreatic cancer that cannot be surgically removed. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that any drugs contraindicated by the protocol that cannot be changed or modified to an acceptable alternative would exclude you from participation. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using the cholesterol-lowering drugs atorvastatin, ezetimibe, and evolocumab (also known as Repatha) together is generally safe and well-tolerated over long periods. Studies have found that these drugs can be combined without major problems. In everyday use, evolocumab has been widely used, and reports of serious side effects are rare.

Atorvastatin and ezetimibe are well-known for lowering cholesterol levels and are usually well-tolerated, with mild side effects like muscle pain or digestive issues being the most common. Evolocumab is a newer drug that also lowers cholesterol but works differently. It is given as a monthly injection.

This combination of drugs is already used to manage cholesterol and protect against heart disease. Researchers are now exploring whether it can help fight pancreatic cancer by depriving cancer cells of cholesterol, potentially slowing or stopping their growth. Although this research is in the early stages, the safety record of these drugs in other uses suggests promising tolerance in this new area. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this treatment because it targets cholesterol metabolism to enhance the effectiveness of chemotherapy for pancreatic cancer. Unlike standard treatments that focus solely on chemotherapy, this approach combines cholesterol-lowering drugs like atorvastatin, ezetimibe, and evolocumab with chemotherapy (FOLFIRINOX). The unique mechanism of disrupting cholesterol pathways may improve the delivery and impact of chemotherapy on cancer cells, offering hope for better outcomes in a notoriously difficult-to-treat cancer.

What evidence suggests that this cholesterol metabolism disruption is effective for pancreatic cancer?

Research has shown that interfering with cholesterol function in the body can slow pancreatic cancer cell growth and increase their responsiveness to chemotherapy. Cholesterol plays a crucial role in the growth and spread of cancer cells, particularly in pancreatic cancer. In this trial, participants will receive a combination of medications—atorvastatin, ezetimibe, and evolocumab—designed to significantly lower cholesterol levels. This treatment aims to deprive cancer cells of the cholesterol they need, slowing their growth and enhancing the effects of standard chemotherapy. This approach is expected to improve pancreatic cancer management by weakening cancer cells and making them more vulnerable. ^{1 3 4 6 7}

Who Is on the Research Team?

Anne Gangloff, MD PhD FRCPC

Principal Investigator

CHU de Québec-Université Laval

Maxime Chénard-Poirier, MD FRCPC

Principal Investigator

CHU de Québec-Université Laval

Félix Couture, MD FRCPC

Principal Investigator

CHU de Québec-Université Laval

Vincent Castonguay, MD FRCPC

Principal Investigator

CHU de Québec-Université Laval

Olivier Dumas, MD FRCPC

Principal Investigator

CHU de Québec-Université Laval

Anne-Marie Carreau, MD FRCPC

Principal Investigator

CHU de Québec-Université Laval

Frédéric Calon, PhD

Principal Investigator

CHU de Québec-Université Laval

Nabil G. Seidah, PhD

Principal Investigator

Institut de recherches cliniques de Montréal

Francine Aubin, MD, FRCPC

Principal Investigator

CHUM

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, untreated advanced pancreatic cancer that can't be removed by surgery or has spread. They must have a life expectancy of at least 12 weeks, good performance status (able to carry out daily activities), and normal organ function. Women who can bear children and men must use effective birth control during the study.

Inclusion Criteria

My pancreatic cancer is advanced and cannot be removed by surgery.

I am considered fit for standard-dose FOLFIRINOX chemotherapy.

Have a life expectancy of at least 12 weeks

Exclusion Criteria

I do not have any uncontrolled infections or bleeding disorders.

I quit smoking more than 3 months ago.

You have had a bad reaction to PCSK9 inhibitors or ezetimibe in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of atorvastatin, ezetimibe, and evolocumab along with standard chemotherapy (FOLFIRINOX)

1 year

Monthly visits for evolocumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cholesterol metabolism disruption

Trial Overview The study tests if adding cholesterol-lowering drugs (atorvastatin, ezetimibe, Repatha) to standard chemotherapy (FOLFIRINOX) slows down or stops pancreatic cancer progression. It's a proof-of-concept trial aiming to see if this combination is feasible and acceptable for patients.

How Is the Trial Designed?

Group I: Multipathway cholesterol metabolism disruption Experimental Treatment 1 Intervention

Twelve to fifteen patients will receive a combination of daily atorvastatin 40 mg, twice daily ezetimibe 10 mg and evolocumab 420 mg subcutaneously every month. This multipathway cholesterol metabolism disruption will be combined to standard chemotherapy (FOLFIRINOX).

Who Is Running the Clinical Trial?

CHU de Quebec-Universite Laval

Lead Sponsor

Trials

177

Recruited

110,000+

Biovalorem

Collaborator

Trials

1

Recruited

3+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10650553/

Cholesterol Metabolism in Pancreatic Cancer - PMC Combination therapies of statins and bisphosphonates have also demonstrated improved outcomes [74]. Clinical trials are currently investigating ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04862260

Study Details | NCT04862260 | Cholesterol Disruption in ... It is expected that a drug-induced cholesterol shortage will slow-down or stop the progression of pancreatic adenocarcinomas while increasing the response to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10229316/

The evolving landscape of PCSK9 inhibition in cancer - PMC This review examines the current evidence regarding the effects of PCSK9 inhibition in the context of different cancers and cancer-associated complications.

4. withpower.com withpower.com/trial/cholesterol-lowering-drug-chemotherapy-for-pancreatic-cancer-aa29b

Cholesterol-Lowering Drug + Chemotherapy for Pancreatic ... Research shows that disrupting cholesterol metabolism can slow the growth of pancreatic cancer cells and make them more sensitive to chemotherapy. Studies found ...

5. mdpi.com mdpi.com/1424-8247/17/3/364

Adverse Reactions to Evolocumab: Analysis of Real-World ... The active principle evolocumab has shown significant efficacy in reducing C-LDL levels by up 75%; this result has been confirmed by a phase 3 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10974070/

Adverse Reactions to Evolocumab: Analysis of Real-World ... The purpose of this study is to update knowledge of the safety of evolocumab through an analysis of post-marketing real-world data on suspected adverse ...

7. jmcp.org jmcp.org/doi/10.18553/jmcp.2016.22.6.641

A Systematic Review of PCSK9 Inhibitors Alirocumab and ... Although there is strong evidence that alirocumab lowers lipids significantly, there is currently no evidence of a benefit in cardiovascular outcomes when ...