Namodenoson for Liver Cancer

(LIVERATION Trial)

Recruiting at 65 trial locations

Overseen By Zivit Harpaz

Age: 18+

Sex: Any

Trial Phase: Phase 3

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) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Indefinite, until disease progression or unacceptable adverse events

471 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, namodenoson, for individuals with advanced liver cancer, specifically hepatocellular carcinoma, who have not responded to initial treatments. The goal is to evaluate the effectiveness and safety of namodenoson compared to a placebo (a non-active substance). Suitable participants include those with advanced liver cancer that has not improved with at least one prior treatment and have cirrhosis classified as Child-Pugh Class B7. As a Phase 3 trial, this study is the final step before potential FDA approval, offering participants an opportunity to contribute to the development of a promising new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that namodenoson is generally safe based on past studies. In earlier research, patients tolerated namodenoson well, and it demonstrated positive safety results. No major safety issues were reported. This suggests the drug might be safe for people. However, all medications can have side effects, which can vary from person to person. Always consult a doctor about any concerns before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver cancer?

Namodenoson is unique because it targets the A3 adenosine receptor, a mechanism not commonly addressed by existing liver cancer treatments like sorafenib or lenvatinib, which primarily inhibit various kinases. This selective targeting could potentially lead to a better safety profile with fewer side effects, as it aims to minimize the impact on healthy cells while focusing on cancerous ones. Researchers are excited because this specific action might not only improve effectiveness in slowing disease progression but also enhance patients' quality of life during treatment.

What evidence suggests that namodenoson might be an effective treatment for liver cancer?

Research has shown that namodenoson, a type of medication, offers promising results in treating advanced liver cancer, known as hepatocellular carcinoma (HCC). In earlier studies, patients with HCC who took namodenoson experienced better outcomes than those who did not. Namodenoson targets specific parts of the body to combat cancer cells and reduce inflammation. Early evidence suggests it may slow the disease in patients who have already tried other treatments. In this trial, participants will receive either namodenoson or a placebo to further evaluate its effectiveness as a treatment option for advanced liver cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Michael H Silverman, MD

Principal Investigator

BioStrategics Consulting Ltd

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Namodenoson
• Placebo

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.

How Is the Trial Designed?

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

Namodenoson is already approved in European Union, United States for the following indications:

Approved in European Union as Namodenoson for:

• None (currently in Phase III trials for hepatocellular carcinoma)

Approved in United States as Namodenoson for:

• None (currently in Phase III trials for hepatocellular carcinoma)

Who Is Running the Clinical Trial?

Can-Fite BioPharma

Lead Sponsor

Trials

21

Recruited

3,600+

Published Research Related to This Trial

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]

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]

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]

Citations

1. esmed.org esmed.org/MRA/mra/article/download/6343/99193548978/

Cardio- and Hepato- Protective Effects of Namodenoson ... Namodenoson is currently under clinical development as a treatment for hepatocellular carcinoma. (phase 3 trial is ongoing) and metabolic ...

2. researchgate.net researchgate.net/publication/333409474_2503_A_phase_II_randomized_double-blind_placebo-controlled_trial_evaluating_efficacy_and_safety_of_namodenoson_CF102_an_A_3_adenosine_receptor_agonist_A_3_AR_as_a_second-line_treatment_in_patients_wit

[2503] A phase II, randomized, double-blind, placebo ... We present the results of a double blind, randomized phase 2, placebo-controlled study (NCT02128958), assessing the efficacy and safety of ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38672201/

Namodenoson at the Crossroad of Metabolic Dysfunction- ... Namodenoson (CF102) is a small, orally available, anti-inflammatory, and anti-cancer drug candidate currently in phase 2B trial for the treatment of metabolic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7825785/

Namodenoson in Advanced Hepatocellular Carcinoma and ... Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05201404

Study Details | NCT05201404 | Namodenoson in the ... The trial will evaluate the efficacy and safety of namodenoson as compared to placebo. Detailed Description. This is a multicenter, randomized, double-blind, ...