Hepatocellular CarcinomaPhase 2NCT03219372
Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence
A Phase 2 study testing Pravastatin Pill in people with Hepatocellular Carcinoma and Liver Cirrhoses, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
Hepatocellular Carcinoma (HCC) is a major health concern in the United States, particularly among people with liver cirrhosis. Out of every 100 patients with liver cancer, only 18 will survive 5 years or more. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Liver Cirrhoses
- What is being tested?
- Pravastatin Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Sep 2018to 5 Mar 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Confirmed diagnosis of liver cirrhosis (Child-Pugh A or B) assessed by the presence of clinical signs, symptoms, body imaging, or liver biopsy
- Diagnosis of HCC falling within one of the following criteria prior to LRT. Criteria fulfillment will be confirmed by the Imaging Charter and MedQIA.
- One lesion ≤ 5 cm or two to three lesions, each ≤ 3 cm.
- One lesion > 5 cm and ≤ 8 cm.
- Two or three lesions, of which at least one is > 3 cm and all are ≤ 5 cm each. The sum of all diameters must be ≤ 8 cm.
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- Four or five lesions, each < 3 cm. The sum of all diameters must be ≤ 8 cm.
- Initiation of LRT (according to clinical judgement) within 24 months prior to Screening Visit, with adequate response as determined by Imaging Charter and MedQIA.
- ECOG performance status ≤1 (Karnofsky ≥70%; see Appendix A)
- AST (SGOT) \& ALT (SGPT) ≤5 × institutional ULN
- AFP < 400 ng/mL
- Ability to understand and the willingness to sign a written informed consent document and medical release
- Agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; for women who are able to become pregnant.
- Willing and able to comply with trial protocol and follow-up
Who cannot join
- Current use of statin medication or statin use within 12 months of Screening visit.
- Current systemic use of medications known to interact with statins and potentially increase toxicity, including (e.g., gemfibrozil, cyclosporine, clarithromycin, colchicine, niacin and fibrates).
- History of adverse effects, intolerance, or allergic reactions attributed to compounds of similar chemical or biologic composition to pravastatin (i.e., other statin medications)
- Current use of any other investigational agents
- Women who are pregnant. Women who are able to become pregnant must have a confirmed negative pregnancy test prior to enrollment.
- Women who are breastfeeding. It is not known whether pravastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pravastatin, breastfeeding should be discontinued if the mother is treated with pravastatin.
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- Prior liver transplant
- MELD score ≥30.
- History of chronic myopathy
- Active malignancy within the past 5 years (excluding HCC, basal/squamous cell skin cancer, or prostate cancer with a Gleason score 6 or less)
- Known HIV infection
- Hemophilia
- Concurrent illness which in the opinion of the investigators would compromise either the patient or the integrity of the data
- Concurrent excessive alcohol consumption (average alcohol consumption of more than 5 drinks per day)
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Hepatocellular Carcinoma (HCC) is a major health concern in the United States, particularly among people with liver cirrhosis. Out of every 100 patients with liver cancer, only 18 will survive 5 years or more. While locoregional therapies are utilized in an effort to combat this disease, the recurrence rate of HCC after these therapies are high.
Statins are widely used drugs that lower cholesterol levels. Some studies have suggested that statins lower risk of HCC recurrence, but this possibility has not been studied thoroughly in a clinical trial. This study will examine the effects of pravastatin, a type of statin, on time to HCC recurrence in patients with early stage HCC. It is possible that pravastatin in combination with locoregional therapies may delay or protect against HCC recurrence.
Read the detailed description
To date, there has been a scarcity of clinical trials evaluating the effectiveness of adjuvant therapies in patients with early stage HCC, although it is widely considered an area of highly unmet need.
The objective of this randomized double-blinded, placebo-controlled Phase II trial is to examine the effects of pravastatin use versus placebo after 12 months of treatment on hepatocellular cancer (HCC) recurrence in 130 patients with liver cirrhosis, HCC meeting Milan Criteria or OPTN tumor downstaging criteria for tumor burden, and initial locoregional therapy (LRT) with adequate response.
- Conditions
- Hepatocellular Carcinoma, Liver Cirrhoses
- Being tested
- Pravastatin Pill, Placebo Oral Tablet
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pravastatin PillDrug
Also called statin
statin
Placebo Oral TabletDrug
Also called placebo
placebo
| Study group | Role | What they receive |
|---|---|---|
| Pravastatin Pill | Experimental | Daily pravastatin (40mg) Receives: Drug: Pravastatin Pill |
| Placebo Oral Tablet | Placebo comparator | Placebo Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Recurrence
Mean difference in time (in months) from baseline (study visit 1) to first hepatocellular cancer (HCC) recurrence or HCC death within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.
- HCC recurrence will be confirmed by central expert independent radiographic review.
Measured: 12 months from baseline
Secondary outcomes (7)
Recurrence Free Survival
Mean difference in time (in months) from baseline (study visit 1) to first occurrence of a documented hepatocellular cancer (HCC) recurrence within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.
- HCC recurrence will be confirmed by central expert independent radiographic review.
Measured: 12 months from baseline
Overall Survival
Mean difference in time (in months) from baseline (study visit 1) to death (for any reason) within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.
Measured: 12 months from baseline
Waitlist Drop-off
Mean difference in time from baseline (study visit 1) to liver transplant waitlist drop-off within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.
Measured: 12 months from baseline
Change in Liver Stiffness
Mean difference in mean change in liver stiffness (as measured by MRE or FibroScan) between baseline (study visit 1) and 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.
Measured: 12 months from baseline
Change in Liver Fat Fraction
Mean difference in within-person change in liver fat fraction (as measured by MRE) between baseline (study visit 1) and 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.
Measured: 12 months from baseline
Change in Serum Biomarkers of Monocyte/Macrophage and Stellate Cell Activation
Mean difference in serum biomarkers including cytokines, chemokines, soluble receptors, and proteins (eg. IL6, TNFα, sTNFRII, IL18BP, sCD163, IL10, IL17, IL-8, CCL17, TGFβ) from baseline (study visit 1) to 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.
Measured: 12 months from baseline
Levels of Liver Tissue Markers Related to HCC
Mean difference in liver tissue markers related to HCC including those in the Wnt/β-catenin pathway (eg. β-catenin, glutamine synthetase) from baseline (study visit 1) to 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.
Measured: 12 months from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2017
- Study start27 Sep 2018
- Primary completion4 Dec 2018
- Study completion5 Mar 2019
Why it stopped: Study discontinued due to low accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 drug versus placebo
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Shehnaz Hussain, Cedars-Sinai Medical Center
- Investigators
- Shehnaz Hussain, PhD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03219372
- Sponsor's protocol ID
- IIT2017-08-HUSSAIN-STATLV
- Other IDs
- 1R01CA218486-01
- Status last verified
- Dec 2020
- First submitted
- 13 Jul 2017
- Last updated
- 22 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence
- ClinicalTrials.gov ID
- NCT03219372
- Acronym / sponsor ID
- IIT2017-08-HUSSAIN-STATLV
- Conditions
- Hepatocellular Carcinoma, Liver Cirrhoses
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study discontinued due to low accrual.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 27 Sep 2018 (actual)
- Primary completion
- 4 Dec 2018 (actual)
- Study completion
- 5 Mar 2019 (actual)
- First posted
- 17 Jul 2017 (actual)
- Results
- Posted 22 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hepatocellular Carcinoma (HCC) is a major health concern in the United States, particularly among people with liver cirrhosis. Out of every 100 patients with liver cancer, only 18 will survive 5 years or more. While locoregional therapies are utilized in an effort to combat this disease, the recurrence rate of HCC after these therapies are high.
Statins are widely used drugs that lower cholesterol levels. Some studies have suggested that statins lower risk of HCC recurrence, but this possibility has not been studied thoroughly in a clinical trial. This study will examine the effects of pravastatin, a type of statin, on time to HCC recurrence in patients with early stage HCC. It is possible that pravastatin in combination with locoregional therapies may delay or protect against HCC recurrence.
Detailed description
To date, there has been a scarcity of clinical trials evaluating the effectiveness of adjuvant therapies in patients with early stage HCC, although it is widely considered an area of highly unmet need.
The objective of this randomized double-blinded, placebo-controlled Phase II trial is to examine the effects of pravastatin use versus placebo after 12 months of treatment on hepatocellular cancer (HCC) recurrence in 130 patients with liver cirrhosis, HCC meeting Milan Criteria or OPTN tumor downstaging criteria for tumor burden, and initial locoregional therapy (LRT) with adequate response.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 1:1 drug versus placebo
| Arm | Type | Receives |
|---|---|---|
| Pravastatin Pill | Experimental | Drug: Pravastatin PillDaily pravastatin (40mg) |
| Placebo Oral Tablet | Placebo comparator | Drug: Placebo Oral TabletPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age ≥18 years
- Confirmed diagnosis of liver cirrhosis (Child-Pugh A or B) assessed by the presence of clinical signs, symptoms, body imaging, or liver biopsy
- Diagnosis of HCC falling within one of the following criteria prior to LRT. Criteria fulfillment will be confirmed by the Imaging Charter and MedQIA.
- Initiation of LRT (according to clinical judgement) within 24 months prior to Screening Visit, with adequate response as determined by Imaging Charter and MedQIA.
- ECOG performance status ≤1 (Karnofsky ≥70%; see Appendix A)
Key exclusion criteria (14 listed)
- Current use of statin medication or statin use within 12 months of Screening visit.
- Current systemic use of medications known to interact with statins and potentially increase toxicity, including (e.g., gemfibrozil, cyclosporine, clarithromycin, colchicine, niacin and fibrates).
- History of adverse effects, intolerance, or allergic reactions attributed to compounds of similar chemical or biologic composition to pravastatin (i.e., other statin medications)
- Current use of any other investigational agents
- Women who are pregnant. Women who are able to become pregnant must have a confirmed negative pregnancy test prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pravastatin PillAlso: statinstatin | Drug | Pravastatin Pill |
| Placebo Oral TabletAlso: placeboplacebo | Drug | Placebo Oral Tablet |
Primary outcome
Time to Recurrence
Time frame: 12 months from baseline
Mean difference in time (in months) from baseline (study visit 1) to first hepatocellular cancer (HCC) recurrence or HCC death within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo. - HCC recurrence will be confirmed by central expert independent radiographic review.
7 secondary outcomes
Recurrence Free Survival
Time frame: 12 months from baseline
Overall Survival
Time frame: 12 months from baseline
Waitlist Drop-off
Time frame: 12 months from baseline
Change in Liver Stiffness
Time frame: 12 months from baseline
Change in Liver Fat Fraction
Time frame: 12 months from baseline
Change in Serum Biomarkers of Monocyte/Macrophage and Stellate Cell Activation
Time frame: 12 months from baseline
Levels of Liver Tissue Markers Related to HCC
Time frame: 12 months from baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shehnaz Hussain, PhD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pravastatin Pill in people with Hepatocellular Carcinoma and Liver Cirrhoses, run by Cedars-Sinai Medical Center at 1 site in United States.
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 14 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: stopped early, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Recurrence (time frame: 12 months from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jan 2021.