LIVERATION: Namodenoson in the Treatment of Advanced Hepatocellular Carcinoma in Patients With Child-Pugh Class B7 Cirrhosis

Sponsor

Can-Fite BioPharma (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05201404

Collaborator

(none)

471

Enrollment

Locations

Arms

Anticipated Duration (Months)

18.8

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a clinical trial in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh Class B7 (CPB7) cirrhosis whose disease has progressed on at least 1st-line therapy. The trial will evaluate the efficacy and safety of namodenoson as compared to placebo.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Cirrhosis	Drug: Namodenoson Drug: Placebo	Phase 3

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled clinical trial in patients with advanced HCC and CPB7 cirrhosis whose disease has progressed on at least 1st-line therapy. The trial will evaluate the efficacy and safety of namodenoson as compared to placebo. Patients will be randomly assigned in a 2:1 ratio to treatment with oral doses of either namodenoson 25 mg or matching placebo administered twice daily for consecutive 28-day cycles. Patients will be evaluated regularly for safety. Tumor imaging will be performed every two cycles. Treatment will continue until the patient experiences PD or unacceptable drug-related intolerability. Patients will return for a follow-up visit 28 days after completion of the last dose of study drug, and survival data will be obtained for all randomized patients who consent to long-term follow-up. Patients who discontinue dosing and consent to follow-up will be followed indefinitely for survival status.

Once the requisite number of events has been observed and the blind is broken for analysis of the trial results, any surviving patients who remain on blinded drug will be offered the opportunity to continue dosing with OL namodenoson 25 mg twice daily indefinitely.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

471 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel group, double-blinded, randomization in a 1:1 ratio to active versus placeboParallel group, double-blinded, randomization in a 1:1 ratio to active versus placebo

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Namodenoson in the Treatment of Advanced Hepatocellular Carcinoma in Patients With Child-Pugh Class B7 Cirrhosis

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Namodenoson (CF102) Namodenoson 25 mg orally BID, until disease progression or unacceptable adverse events	Drug: Namodenoson Adenosine A3 Receptor (A3AR) agonist Other Names: CF102
Placebo Comparator: Placebo Matching placebo orally BID, until disease progression or unacceptable adverse events	Drug: Placebo Control arm Other Names: Inactive control

Arm

Intervention/Treatment

Experimental: Namodenoson (CF102)

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

Drug: Namodenoson

Adenosine A3 Receptor (A3AR) agonist

Other Names:

CF102

Placebo Comparator: Placebo

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

Drug: Placebo

Control arm

Other Names:

Inactive control

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [From the time of randomization until the date of death from any cause, assessed up to 60 months]
Median duration of survival

Secondary Outcome Measures

Progression-Free Survival (PFS) [From the time of randomization until the date of disease progression or death from any cause, assessed up to 60 months]
Median time to disease progression using RECIST and modified RECIST criteria
Objective Response Rate (ORR) [Through study completion, with a median of 9 months]
Proportion of patients who experience Objective Response (OR) using RECIST and modified RECIST criteria
Incidence and nature of treatment-emergent adverse events [Through study completion, with a median of 9 months]
Incidence and nature of treatment-emergent adverse events as assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5)
Pharmacokinetics (PK) of namodenoson in this population [29 days]
Plasma concentration of namodenoson

Other Outcome Measures

Duration Of Response (DOR) [Through study completion, with median of 9 months]
Time from first response (CR or PR) to progression or death, whichever occurs first
Disease Control Rate (DCR) [Through study completion, with median of 9 months]
Proportion of patients who experience OR as well as those who experience Stable Disease (SD) for at least four treatment cycles, ie, four months
Quality of Life (QOL) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) [Through study completion, with a median of 9 months]
Assess QOL in this population using the EORTC QLQ-C30, a 30-item questionnaire. Each question is measured in a range in score from 0 to 100. A high scale score represents a higher response level.
Quality of Life (QOL), using the hepatocellular carcinoma- (HCC-) specific module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question Module (EORTC QLQ-HCC18) [Through study completion, with a median of 9 months]
Assess QOL in this population using the HCC-specific module of the EORTC QLQ-HCC18, an 18-item questionnaire. Each question is measured in a range in score from 0 to 100. A high scale score represents a higher response level.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males and females at least 18 years of age.
Diagnosis of HCC:

For patients without cirrhosis at the time of diagnosis, histologic confirmation is required (archival tissue is acceptable).
For patients with underlying cirrhosis at the time of diagnosis, diagnosis of HCC established according to the American Association for the Study of Liver Diseases Practice Guideline algorithm (Marrero 2018).

HCC is advanced (i.e., treatment-refractory or metastatic) and no standard therapies are expected to be curative.
HCC has progressed on at least 1, but no more than 2, prior systemic treatment regimens; prior locoregional therapy is allowed.
Barcelona Clinic Liver Cancer (BCLC) Stage B or C (Llovet 1999).
Prior HCC treatment was discontinued for at least 2 weeks prior to the Baseline Visit.
Measurable disease by RECIST v1.1 (Eisenhauer 2009).
ECOG PS of ≤ 1.
Cirrhosis classified as CPB7; if ascites is used as a scoring criterion, it must be classified as Grade ≥2 by the Clinical Practice Guidelines of the European Association for the Study of the Liver (EASL 2010).
The following laboratory values must be documented within ten days prior to the first dose of study drug:

Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
Platelet count at least 75 × 10^9/L
Creatinine clearance at least 50 mg/dL (estimated glomerular filtration rate by the Cockcroft-Gault or the Modification of Diet in Renal Disease methods)
AST and ALT ≤ 5 × the upper limit of normal (ULN)
Total bilirubin ≤ 3.0 mg/dL
Serum albumin ≥ 2.8 g/dL.

Life expectancy of ≥ 6 weeks.
For women of childbearing potential, negative serum pregnancy test result.
Provide written informed consent to participate.
Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other trial-related procedures.

Exclusion Criteria:

Receipt of >2 prior systemic drug therapies for HCC.
Receipt of systemic cancer therapy, immunomodulatory drug therapy, immunosuppressive therapy, or corticosteroids > 20 mg/day prednisone or equivalent within 14 days prior to the Baseline Visit or concurrently during the trial.
Locoregional treatment within 4 weeks prior to the Baseline Visit.
Major surgery or radiation therapy within 4 weeks prior to the Baseline Visit.
Use of any investigational agent within 4 weeks prior to the Baseline Visit.
Concomitant use of P-glycoprotein (P-gp)/breast cancer resistance protein (BCRP) inhibitors and/or substrates with a narrow therapeutic index unless the medication can be taken at least 3 hours before or after taking the investigational product (see Section 12.2).
Child-Pugh Class A, B8/9, or C cirrhosis.
Hepatic encephalopathy.
Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusion within 4 weeks prior to the Baseline Visit.
Uncontrolled or clinically unstable thyroid disease, per judgment of the Principal Investigator.
Active bacterial, viral, or fungal infection requiring systemic therapy or operative or radiological intervention.
Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness.
Liver transplant.
Active malignancy other than HCC.
Uncontrolled arterial hypertension or congestive heart failure (New York Heart Association Classification 3 or 4).
Angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
History of, or ongoing, cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to > 470 msec (patients with bundle branch block will not be excluded for QTc reasons).
Pregnant or lactating female.
Women of childbearing potential, unless they agree to use dual contraceptive methods which, in the opinion of the Investigator, are effective and adequate for the patient's circumstances while on study drug.
Men who partner with a woman of childbearing potential, unless they agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable, or barrier method) while on study drug and for 3 months afterward.
Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with trial participation or study drug administration; may interfere with the informed consent process and/or with compliance with the requirements of the trial; or may interfere with the interpretation of trial results and, in the Investigator's opinion, would make the patient inappropriate for entry into this trial.

Contacts and Locations

Locations

	Site	City	Country
1	University Clinical Centre of Republic of Srpska	Banja Luka	Bosnia and Herzegovina
2	University Clinical Hospital Mostar	Mostar	Bosnia and Herzegovina
3	University Clinical Centre of Republic of Srpska	Sarajevo	Bosnia and Herzegovina
4	Department of Medical Oncology, Complex Oncology Center - Burgas EOOD	Burgas	Bulgaria
5	First Department of Medical Oncology, Gastroenterology and Pulmology, Complex Oncology Center - Plovdiv EOOD, Plovdiv	Plovdiv	Bulgaria
6	Medical Center Leo Clinic EOOD Plovdiv	Plovdiv	Bulgaria
7	Medical Oncology Department, University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD, Sofia	Sofia	Bulgaria
8	Rabin Medical Center Beilinson Hospital	Petach Tikva	Israel
9	IMSP Institute of Oncology	Chisinau	Moldova, Republic of
10	Szpital Wojewodzki	Olsztyn	Poland
11	Institutul Regional de Gastroenterologie si Hepatologie	Cluj-Napoca	Romania
12	IOCN, Medical Oncology	Cluj-Napoca	Romania
13	Spitalul Clinic Judetean de Urgenta Constanta Oncology Dept	Constanţa	Romania
14	Oncolab SRL	Craiova	Romania
15	Oncology Center "Sf. Nectarie" Medical Oncology	Craiova	Romania
16	Euroclinic lasi	Iaşi	Romania
17	IRO iasi-Clinica Oncologie Medicala	Iaşi	Romania
18	Spitalul Clinic Pelican Oradea Oncology Department	Oradea	Romania
19	Oncocenter Oncologie Clinica SRL	Timişoara	Romania
20	Oncomed - Medical Oncology	Timişoara	Romania
21	Clinic for Gastroenterology and Hepatology, Military Medical Academy	Belgrade	Serbia
22	Oncology Department, Health Center Kladovo	Kladovo	Serbia
23	University Clinical Centre Kragujevac, Department of Oncology	Kragujevac	Serbia
24	Oncology Institute of Vojvodina	Sremska Kamenica	Serbia
25	Onkologická klinika SZU a FNsP FDR Banská Bystrica	Banská Bystrica	Slovakia