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Pancreatic Ductal AdenocarcinomaEarly Phase 1NCT04862260

Cholesterol Disruption in Combination With the Standard of Care in Patients With Advanced Pancreatic Adenocarcinoma

A Early Phase 1 study testing Cholesterol metabolism disruption in people with Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer, run by CHU de Quebec-Universite Laval at 2 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Cardiovascular diseases and cancers, the two leading causes of death in Canada, require cholesterol to sustain their progression. All cells require cholesterol, but cancer cells have much higher needs to sustain growth, division and metastasis. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Cholesterol metabolism disruption
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
2 sitesCanada
Study dates
4 Oct 2021to 31 Dec 2026
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • To be eligible to this trial, patients must fulfill the following inclusion criteria:
  • Have a histologically confirmed, treatment-naive locally advanced and inoperable (LaiPDAC) or metastatic pancreatic ductal adenocarcinoma (mPDAC).
  • Be at least 18 years or older at the time of signing the informed consent.
  • Have a life expectancy of at least 12 weeks.
  • Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
  • Have measurable disease as assessed by RECIST v1.1.
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  • Agrees and amenable to a tumor (if deemed safe only) and liver biopsy (all participants) at baseline and on day 42 +/- 3 days. Patient that are anticoagulated at baseline are eligible provided it is deemed safe by the investigator to stop anticoagulation momentarily in order to safely proceed to a biopsy.
  • Eligible to standard-dose FOLFIRINOX as assessed by the principal investigator or a sub-investigator. FOLFIRINOX doses can be adapted according to SOC.
  • Demonstrate normal organ function as defined below. These assessments must be done within 7 days of Cycle 1 Day-7.
  • Hemoglobin (Hb) ≥ 90 g/L Absolute neutrophil count ≥ 1.5 x 10 9/L Platelet count ≥ 100 x 10 9/L INR ≤ 1.3 (unless patient is anticoagulated) aPTT ≤ 1.5 x ULN (switching to LMWH will be recommended) Total bilirubin ≤ 1.5 x ULN OR Direct bilirubin (for patients with total bilirubin ≥ 1.5 x ULN) AST and ALT ≤ 3 x ULN CPK ≤ 1.5 x ULN Serum creatinine ≤ 1.5 x ULN OR Estimated GFR (as per institutional standards) ≥ 50 ml/min
  • Provide written informed consent and able to follow the trial treatment and visit schedule.
  • For Women Of Child-Bearing Potential (WOCBP), a negative serum pregnancy test must be obtained prior to receiving the study medication.
  • WOCBP should agree to use 2 different methods of birth control OR abstain from heterosexual intercourse for the duration of the trial and up to 90 days after the last study medication administration.
  • Male subjects should agree to use an adequate method of contraception for the duration of the trial and up to 90 days after the last study medication administration. Male subjects should refrain from donating sperm during this period.

Who cannot join

  • To be eligible to this trial, patients must not fulfill any of the following exclusion criteria:
  • Locally advanced pancreatic ductal adenocarcinoma deemed operable.
  • Any pancreatic ductal adenocarcinoma deemed operable or borderline operable that can be treated with neoadjuvant chemotherapy.
  • Known additional malignancy that is progressing or that requires treatment. Exceptions include basal cell carcinoma of the skin, in situ bladder or in situ cervical cancer. Other malignancy may be eligible after consultation with the promotor-investigator.
  • Spinal cord compression or brain metastases unless treated, stable and not requiring steroids for at least 4 weeks prior to the initiation of study treatment.
  • Baseline myalgia or myositis of any etiology.
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  • Prior treatment with FOLFIRINOX in the adjuvant setting.
  • History of clinically significant intolerance or myositis with any statin.
  • History of clinically significant intolerance or hypersensitivity to PCSK9 inhibitors or ezetimibe.
  • Baseline grade ≥ 2 ULN Creatine Phosphokinase (CPK) elevation.
  • Liver tumor burden that is deemed unsafe by the investigator.
  • Major surgery or procedure from which the patient has not yet recovered.
  • Any medical condition that puts the patient at high medical risk, including but not limited to active uncontrolled infection or active bleeding diathesis.
  • Any history of disease that, in the opinion of the investigator, puts liver function at risk including but not limited to autoimmune hepatitis or history of hepatitis B, hepatitis C or human immunodeficiency virus (HIV). Screening at baseline for those conditions is not required.
  • Use of any drugs that are contraindicated as per protocol and that cannot be changed or modified to an acceptable alternative.
  • Active smoker. Complete usage of tobacco must have been stopped for at least 3 months.
  • Abnormally low hematocrit, as assessed by the oncologist.

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

  • CHUM

    Montreal, Quebec, H2X 0A9

  • CHU de Québec-Université Laval

    Québec, Quebec, G1R 2J6

Other trials in Canada

About this study

Official title: A Phase 1 Feasibility Study of Cholesterol Metabolism Reprogramming (Evolocumab, Atorvastatin and Ezetimibe) in Combination With the Standard of Care in Patients With Advanced or Metastatic Pancreatic Adenocarcinoma

Cardiovascular diseases and cancers, the two leading causes of death in Canada, require cholesterol to sustain their progression. All cells require cholesterol, but cancer cells have much higher needs to sustain growth, division and metastasis. The availability of new cholesterol-lowering drugs developed to protect patients from heart diseases has resulted in unprecedented low levels of cholesterol. The combination of atorvastatin, ezetimibe and Repatha, which are 3 cholesterol-lowering drugs used in combination, is safe, well tolerated and efficient over years of treatment. Recent reports indicate that abundant cholesterol supplies are required to sustain the progression of pancreatic ductal adenocarcinomas. This proof-of-concept study aims to verify the feasibility, the acceptability and gain preliminary data on adding a cholesterol shortage on top of FOLFIRINOX (standard chemotherapy) in newly diagnosed patients with locally advanced pancreatic adenocarcinomas or metastatic pancreatic adenocarcinomas. It is expected that a drug-induced cholesterol shortage will slow-down or stop the progression of pancreatic adenocarcinomas while increasing the response to chemotherapy.

Being tested
Cholesterol metabolism disruption
Keywords
Statin, Atorvastatin, Lipitor, PCSK9 monoclonal antibody, PCSK9 inhibitor, PCSK9, Evolocumab, Repatha, Alirocumab, Praluent, Lipid droplets and vacuoles, NPC1L1 transporter, HMG Co A reductase, LDL receptor, LRP1 receptor, SRB1 receptor, Lipids, Cancer, Cholesterol, Pancreas cancer
Medical subject headings
Pancreatic Neoplasms, Neoplasm Metastasis, Hyperlipoproteinemia Type II, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cholesterol metabolism disruptionDrug

    Also called A combination of a lipophilic statin (Atorvastatin, Lipitor), a NPC1L1 inhibitor (Ezetimibe, Ezetrol) and a PCSK9 inhibitor (Evolocumab, Repatha) with chemotherapy in pancreatic cancer

    Cholesterol metabolism disruption using a combination of atorvastatin, ezetimibe and evolocumab in metastatic pancreatic adenocarcinomas

Study groups in NCT04862260
Study groupRoleWhat they receive
Multipathway cholesterol metabolism disruptionExperimentalTwelve 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).
Receives: Drug: Cholesterol metabolism disruption

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety as measured by the rate of adverse events

    To determine causality and grading severity of each adverse event (AEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: 2 years

  2. Characterization of dose-limiting toxicities

    To determine the dose at which no more than 1 out of 6 patients experience a drug related dose-limiting toxicity. To confirm that the combination of daily atorvastatin 40 mg, ezetimibe 10 mg twice daily and monthly evolocumab 420 mg meets the criterion to be the recommended phase II dose (RP2D).

    Measured: 2 years

Secondary outcomes (8)

  1. LDLR (low-density lipoprotein receptor) tumoral and hepatic changes in response to the multipathway cholesterol embargo.

    Assessment of the level of LDLR in the tumor (hepatic metastasis ) and the liver by immunohistochemistry.

    Measured: 1 year

  2. LRP1 (Low-density lipoprotein Receptor-Related Protein 1) tumoral and hepatic changes in response to the multipathway cholesterol embargo.

    Assessment of the level of LRP1 in the tumor (hepatic metastasis ) and the liver by immunohistochemistry.

    Measured: 1 year

  3. NPC1L1 (Niemann-Pick C1-Like 1 protein) tumoral and hepatic changes in response to the multipathway cholesterol embargo.

    Assessment of the level of NPC1L1 in the tumor (hepatic metastasis ) and the liver by immunohistochemistry.

    Measured: 1 year

  4. SRB1 (Scavenger Receptor class B type 1) tumoral and hepatic changes in response to the multipathway cholesterol embargo.

    Assessment of the level of SRB1 in the tumor (hepatic metastasis ) and the liver by immunohistochemistry.

    Measured: 1 year

  5. MHC-1 (Major Histocompatibility Complex class 1) tumoral and hepatic changes in response to the multipathway cholesterol embargo.

    Assessment of the level of MHC-1 in the tumor (hepatic metastasis ) and the liver by immunohistochemistry

    Measured: 1 year

  6. PD-L1 (Programmed Death-Ligand-1) changes in response to the multipathway cholesterol embargo.

    Assessment of the level of PD-L1 (Programmed Death-Ligand-1) in the tumor (hepatic metastasis ) and the liver by immunohistochemistry.

    Measured: 1 year

  7. Change in tumoral and hepatic levels of TILs (Tumor-Infiltrating Lymphocytes)

    Assessment of tumoral and hepatic levels of TILs by immunohistochemistry

    Measured: 1 year

  8. CD36 (Cluster of Differentiation 36) changes in response to the multipathway cholesterol embargo

    Assessment of tumoral and hepatic levels in the tumor (hepatic metastasis ) and the liver by immunohistochemistry.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2021
  2. Study start4 Oct 2021
  3. Primary completion31 Jan 2025
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04862260
Sponsor's protocol ID
CHLOE pancreas
Status last verified
Mar 2026
First submitted
6 Apr 2021
Last updated
19 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Cholesterol metabolism disruption in people with Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer, run by CHU de Quebec-Universite Laval at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety as measured by the rate of adverse events (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04862260.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.

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Clinical Trial NCT04862260 | AzTrials