Namodenoson for Liver Cancer

(LIVERATION Trial)

Recruiting at 55 trial locations

Overseen By Zivit Harpaz

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Can-Fite BioPharma

Must not be taking: Immunosuppressants, Corticosteroids, P-gp/BCRP inhibitors

Disqualifiers: HIV/AIDS, Liver transplant, Hypertension, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests an oral medication on patients with advanced liver cancer who have not responded to previous treatments. The goal is to see if this medication can slow down or stop the growth of cancer cells in the liver. The medication is being developed to treat liver cancer, where longer survival was observed in patients with advanced liver disease.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use certain drugs like systemic cancer therapies, immunosuppressive drugs, or corticosteroids above a certain dose within 14 days before starting the trial. Also, some medications must be timed carefully around the trial drug.

What makes the drug Namodenoson unique for liver cancer treatment?

Namodenoson is unique because it targets specific receptors in the liver, potentially offering a more targeted approach compared to traditional chemotherapy, which often affects the whole body and can cause significant side effects. ^{1 2 3 4 5}

Research Team

Michael H Silverman, MD

Principal Investigator

BioStrategics Consulting Ltd

Eligibility Criteria

Adults with advanced liver cancer (hepatocellular carcinoma) and specific liver cirrhosis (Child-Pugh Class B7), who have tried at least one treatment but no more than two, can join this trial. They should be in a condition to follow the trial procedures and not have had certain treatments or surgeries recently. Women must not be pregnant and participants must agree to use effective contraception.

Inclusion Criteria

My liver condition is classified as moderate.

My liver cancer is advanced and cannot be cured with standard treatments.

I stopped my liver cancer treatment at least 2 weeks ago.

Exclusion Criteria

Presence of severe medical or psychiatric conditions that may increase risk or interfere with trial participation

My liver disease is classified as cirrhosis.

Specific contraceptive requirements for women of childbearing potential and men

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral doses of either namodenoson 25 mg or matching placebo twice daily for consecutive 28-day cycles

Indefinite, until disease progression or unacceptable adverse events

Regular evaluations for safety and tumor imaging every two cycles

Follow-up

Participants return for a follow-up visit 28 days after the last dose of study drug, and survival data is collected

4 weeks

1 visit (in-person)

Open-label extension (optional)

Surviving patients who remain on blinded drug are offered the opportunity to continue dosing with open-label namodenoson 25 mg twice daily indefinitely

Indefinite

Treatment Details

Interventions

• Namodenoson (Other)
• Placebo (Other)

Trial Overview The trial is testing Namodenoson, a new potential drug for advanced liver cancer, against a placebo to see if it's safe and works better. Participants will either receive Namodenoson or a placebo without knowing which one they are getting.

Participant Groups

Group I: Namodenoson (CF102) Experimental Treatment 1 Intervention

Namodenoson 25 mg orally BID, until disease progression or unacceptable adverse events

Group II: Placebo Placebo Group 1 Intervention

Matching placebo orally BID, until disease progression or unacceptable adverse events

Who Is Running the Clinical Trial?

Can-Fite BioPharma

Lead Sponsor

Trials

21

Recruited

3,600+

Findings from Research

In a study involving 25 patients with various liver cancers, 73% of those with colorectal adenocarcinoma showed a positive response to hepatic artery infusion chemotherapy using floxuridine, indicating its efficacy in treating this type of cancer.

The treatment was associated with manageable side effects, such as dyspepsia and elevated liver function tests, and resulted in good quality of life, with median survival for colon cancer patients not yet reached at 16 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic perfusion with FUdR utilizing an implantable system in patients with liver primary cancer or metastatic cancer confined to the liver. Seeger, J., Woodcock, TM., Blumenreich, MS., et al.[2019]

Parenteral 5-fluorouracil (5-FU) is more effective than oral 5-FU for treating metastatic colorectal cancer, but survival rates are similar regardless of the administration schedule (loading, weekly, or continuous infusion).

Regional chemotherapy using intra-arterial infusions of 5-FU shows increased hepatic response rates compared to systemic treatment, but it does not significantly improve survival and carries a risk of considerable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy for colorectal cancer: an overview. Mayer, RJ.[2013]

In a double-blind trial involving 297 patients with Dukes' C colon carcinoma, levamisole was well tolerated, with only four cases of reversible agranulocytosis reported, indicating a relatively safe profile for this treatment.

Despite being well tolerated, levamisole did not show a significant benefit in disease-free survival or overall survival compared to placebo, although the 5-year survival rate was slightly higher in the levamisole group (51% vs. 39%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy of poor prognosis colon cancer with levamisole: results of an EORTC double-blind randomized clinical trial. Arnaud, JP., Buyse, M., Nordlinger, B., et al.[2019]

Adjuvant chemotherapy with 5-FU and levamisole has been shown to significantly reduce relapse and improve survival rates in colon cancer patients, with a 35% reduction in 5-year relapse rates and a 17% reduction in death rates based on studies from 1989 and 1990.

Preliminary data suggest that the combination of 5-FU and folinic acid may be as effective as the standard 5-FU/levamisole treatment, indicating potential alternatives for patients with Dukes stage C colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of colonic carcinoma]. Rochlitz, CF., Herrmann, R.[2013]

NAMI-A, a ruthenium-based compound, effectively reduced lung metastases in mice with advanced mammary carcinoma when administered orally over 11 days, with doses ranging from 150 to 600 mg/kg/day.

The treatment showed no signs of toxicity in the gut or kidneys, indicating that oral administration of NAMI-A could be a safe and effective long-term option for treating tumor-bearing hosts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Effects of the Ruthenium Complex NAMI-A Given Orally to CBA Mice With MCa Mammary Carcinoma. Zorzet, S., Sorc, A., Casarsa, C., et al.[2021]

References

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

Hepatic perfusion with FUdR utilizing an implantable system in patients with liver primary cancer or metastatic cancer confined to the liver. [2019]

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

Systemic therapy for colorectal cancer: an overview. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Adjuvant therapy of poor prognosis colon cancer with levamisole: results of an EORTC double-blind randomized clinical trial. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of colonic carcinoma]. [2013]

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

Pharmacological Effects of the Ruthenium Complex NAMI-A Given Orally to CBA Mice With MCa Mammary Carcinoma. [2021]