Prednisone for Liver Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Theodore Lawrence

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Michigan Rogel Cancer Center

Must be taking: Prednisone

Must not be taking: Antibiotics

Disqualifiers: Uncontrolled infections, Hyperglycemia, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Patients on this study will self administer Prednisone for three days before starting Radiation Therapy (RT) and continue to take 60 mg/day during the first three fractions of RT.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is prednisone generally safe for humans?

Prednisone is generally safe for humans, but it can cause side effects. In a study on liver disease, major side effects were more common with prednisone alone compared to when it was combined with another drug, azathioprine. ^{1 2 3 4 5}

How does the drug prednisone differ from other treatments for liver cancer?

Prednisone is unique because it is a steroid that works by suppressing the immune system and reducing inflammation, which is different from typical cancer treatments that directly target cancer cells. While it is commonly used for autoimmune liver conditions, its use in liver cancer is novel and may focus on managing inflammation rather than directly treating the cancer itself. ^{1 4 6 7 8}

Research Team

Theodore Lawrence

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

This trial is for adults with confirmed hepatocellular carcinoma (HCC) or liver tumors meeting specific criteria. Participants should have recovered from previous liver treatments, have a performance status of ≤2, and meet certain liver function scores (ALBI score ≥ -1.81; CP score ≥ 7). They must understand the study's risks and consent to participate.

Inclusion Criteria

I am 18 years old or older.

I have recovered from my last liver treatment and it's been over 4 weeks since.

I am 18 years old or older.

Exclusion Criteria

I do not have any serious illness that would prevent me from receiving radiation therapy.

My blood sugar levels are not under control.

I have not had any bleeding in my stomach or intestines in the last 30 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants self-administer Prednisone for three days before starting Radiation Therapy

3 days

Radiation Therapy

Participants receive Radiation Therapy while continuing Prednisone for the first three fractions

up to 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including sTNFR1 levels and liver toxicity

6 months

Treatment Details

Interventions

• Prednisone (Corticosteroid)

Trial Overview The study tests if Prednisone can protect the liver when taken three days before and during the first three sessions of Stereotactic Body Radiation Therapy for HCC. Patients will self-administer 60 mg/day of Prednisone in this period.

Participant Groups

Group I: Patients treated with Prednisone Experimental Treatment 1 Intervention

Prednisone will be administered for three days before starting RT, and during the first three fractions of RT. Following an interim analysis of the decrease in sTNFR1 level, a decision will be made whether to administer prednisone for seven days prior to RT, and to continue for additional seven days during RT.

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Marschall S. Runge

University of Michigan Rogel Cancer Center

Chief Executive Officer since 2015

MD, PhD

Eric R. Fearon

University of Michigan Rogel Cancer Center

Chief Medical Officer since 2016

MD, PhD

Findings from Research

In a study of 120 patients with chronic active liver disease, those treated with a combination of prednisone and azathioprine showed better survival rates and resolution of disease symptoms compared to those receiving placebo or higher doses of azathioprine.

The combination therapy (Comb) was found to be the preferred initial treatment because it achieved similar clinical and histological remission rates as prednisone alone, but with fewer major side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared. Summerskill, WH., Korman, MG., Ammon, HV., et al.[2019]

In a study of 50 patients with autoimmune hepatitis, both prednisolone/azathioprine (PRED/AZA) and budesonide/azathioprine (BUD/AZA) showed similar biochemical responses after 6 months of treatment, indicating both regimens are effective.

BUD/AZA had a lower total number of adverse effects compared to PRED/AZA, with no treatment discontinuations in the BUD/AZA group, suggesting it may be a safer first-line treatment option for patients with certain health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and adverse effects of budesonide in remission induction treatment of autoimmune hepatitis: a retrospective study. Binicier, OB., Günay, S.[2020]

In a study of 60 patients with autoimmune hepatitis (AIH) who switched from prednisolone to budesonide, 55% showed a biochemical response after 6 months, increasing to 70% after 12 months, indicating that budesonide can be an effective alternative for those intolerant to prednisolone.

While budesonide treatment was generally well-tolerated with mild side effects, 25% of patients had to revert to prednisolone due to insufficient response or side effects, highlighting the need for close monitoring of treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Limitations of Budesonide as a Second-Line Treatment for Patients With Autoimmune Hepatitis. Peiseler, M., Liebscher, T., Sebode, M., et al.[2019]

Prednisone and its active form, prednisolone, are key treatments for autoimmune hepatitis, working by suppressing immune responses and reducing inflammation in the liver.

Budesonide combined with azathioprine has shown to be more effective and safer than traditional prednisone-based treatments in treatment-naive patients, making it a promising frontline option for noncirrhotic patients with uncomplicated autoimmune hepatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug choices in autoimmune hepatitis: part A--Steroids. Czaja, AJ.[2013]

A study involving over 102,000 subjects in Taiwan found that the use of oral corticosteroids is associated with an increased risk of hepatocellular carcinoma, particularly in individuals with comorbidities like alcohol-related disease, chronic liver disease, and diabetes mellitus.

The risk of developing hepatocellular carcinoma increases with the cumulative duration of oral corticosteroid use, highlighting the need for regular monitoring in high-risk populations, especially those currently using these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic effect of oral corticosteroids use on risk of hepatocellular carcinoma in high risk populations. Lai, SW., Lin, CL., Liao, KF.[2018]

In a study of 28 chronic hepatitis C patients treated with low-dose corticosteroids for over 6 months, there was a significant initial decrease in liver enzymes (transaminases) within the first 3 months, indicating a potential short-term benefit of corticosteroid therapy.

Corticosteroid treatment did not accelerate the progression of chronic hepatitis C, as indicated by a trend towards slower fibrosis progression compared to a control group, suggesting that low-dose corticosteroids may be safe for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does low-dose prolonged steroid therapy affect the natural history of chronic hepatitis C? Romero Gutiérrez, M., del Campo Terrón, S., Moreno Zamora, A., et al.[2014]

Prednisolone (Pred) does not inhibit the antiviral effects of new HCV treatments like asunaprevir (Asu), daclatasvir (Dac), ribavirin (RBV), or interferon-alpha (IFN-α), suggesting it can be safely combined with these therapies after liver transplantation.

However, Pred does reduce the production of IFN-α by plasmacytoid dendritic cells (PDCs), which are important for antiviral responses, indicating that while it doesn't interfere with the drugs' actions, it may impact the immune response in HCV management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prednisolone does not affect direct-acting antivirals against hepatitis C, but inhibits interferon-alpha production by plasmacytoid dendritic cells. de Ruiter, PE., Boor, PP., de Jonge, J., et al.[2021]

In a study of 48 adult patients undergoing orthotopic liver transplantation, switching to low-dose alternate-day prednisone (15 mg) effectively maintained immunosuppression with minimal side effects, as evidenced by a significant reduction in Cushingoid symptoms.

After converting to alternate-day prednisone, only one patient experienced a rejection episode, which was easily managed, indicating that this regimen is both safe and effective for long-term immunosuppression without increasing the dosage of other immunosuppressive medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternate-day prednisone in the maintenance immunosuppressive therapy after orthotopic liver transplantation. Pedrosa, MC., Rohrer, RM., Kaplan, MM.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared. [2019]

2. Croatia pubmed.ncbi.nlm.nih.gov

The efficacy and adverse effects of budesonide in remission induction treatment of autoimmune hepatitis: a retrospective study. [2020]

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

Efficacy and Limitations of Budesonide as a Second-Line Treatment for Patients With Autoimmune Hepatitis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Drug choices in autoimmune hepatitis: part A--Steroids. [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Synergistic effect of oral corticosteroids use on risk of hepatocellular carcinoma in high risk populations. [2018]

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

Does low-dose prolonged steroid therapy affect the natural history of chronic hepatitis C? [2014]

7. Denmark pubmed.ncbi.nlm.nih.gov

Prednisolone does not affect direct-acting antivirals against hepatitis C, but inhibits interferon-alpha production by plasmacytoid dendritic cells. [2021]

8. Denmark pubmed.ncbi.nlm.nih.gov

Alternate-day prednisone in the maintenance immunosuppressive therapy after orthotopic liver transplantation. [2013]