Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

All Drugs and Chemicals

Adenosine

Neurotransmitter Agents

CF102

Michael H Silverman, MD

Salomon Shtemmer, MD

This trial will test the safety and efficacy of CF102 in patients with advanced liver cancer. Successive groups of patients will be given higher doses of CF102 by mouth on a twice-daily basis. Treatment will be assessed for adverse effects and for effects on the tumor.

This is a multicenter, open-label, non-randomized, dose-escalation study, to be conducted in 2 phases: a dose-escalation phase, to determine the MTD of CF102 and to evaluate its safety/tolerability, PK, pharmacodynamic, and preliminary clinical activity; and a dose-confirmation phase, which will be a cohort expansion at or below the MTD (ie, the RP2D) of CF102. Subjects will be treated with oral doses of CF102 in consecutive, 28-day cycles. The initial dose of CF102 will be 1 mg twice daily (BID), with subsequent escalations to 5 and 25 mg BID, unless limited by toxicity. Subjects will be evaluated weekly for the first cycle, every 2 weeks for Cycles 2 and 3, and at the end of each subsequent cycle, up to 6 cycles of CF102 treatment. Subjects will return for a follow-up visit 28 days after completion of the last dose of study drug.

Study Arms: CF102 (1, 5, and 25 mg BID) in 28-day cycles.

A Phase 1-2 Study of CF102 in Patients With Advanced Hepatocellular Carcinoma

A Phase 1-2, Open-label, Dose-escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered CF102 in Patients With Advanced Hepatocellular Carcinoma

Dose-limiting toxicity was defined as a clinically significant AE or laboratory abnormality occurring in Cycle 1

The MTD was defined as the highest dose level at which \< 2 of 6 patients developed Cycle 1 DLT.

Blood samples were collected and plasma concentrations determined using a high-pressure liquid chromatography method.

Therapeutic effect of CF102 in hepatocellular carcinoma measured by number of subjects with objective tumor response

The Peripheral Blood Mononuclear Cells (PBMC) were to be collected at Baseline and Day 28 in order to evaluate the Adenosine A3 receptor (A3AR) and PBMC biomarkers, and clinical effects of CF102.

Can-Fite BioPharma

CF102: CF102 capsules twice daily by mouth

CF102 1mg

CF102 5mg

CF102 25mg

Age, Categorical

Sex: Female, Male

Israel

Region of Enrollment

Sari Fishman, Director of Clincal Trials

Safety Population (all subjects receiving at least one dose of study drug)

Dose Limiting Toxicity

All subjects were evaluated for DLTs in the first cycle of therapy.

Maximum Tolerated Dose

Day 1

Day 29

The first 3 subjects in each dosing cohort participated in the pharmacokinetic sampling.

Maximum Plasma Concentration of CF102 (Cmax)

Number of Subjects With Objective Tumor Response

No data was collected for this exploratory endpoint.

Relationship Between Biomarkers of Peripheral Blood Mononuclear Cell (PBMC) Adenosine A3 Receptor (A3AR) Expression and Clinical Effects of CF102

CF102: CF102 tablets were given orally twice daily

Overall Study

Symptoms and General Pathology

Liver Cirrhosis

Placebo

Michael H Silverman

This is a multicenter, randomized, double-blind, placebo-controlled clinical trial in subjects with advanced HCC and CPB cirrhosis whose disease has progressed while taking 1 prior systemic drug therapy for HCC.

The trial will evaluate the efficacy and safety of CF102 as compared to placebo. Subjects will be randomly assigned in a 2:1 ratio to treatment with oral doses of either CF102 25 mg or matching placebo administered twice daily (BID) for consecutive, 28-day cycles. Subjects will be evaluated regularly for safety. Tumor imaging will be performed every 8 weeks. Treatment will continue until the subject experiences unacceptable drug-related intolerability. Subjects will return for a follow-up visit 28 days after completion of the last dose of study drug, and every attempt will be made to obtain survival data on all randomized subjects. Subjects who discontinue will be followed indefinitely for survival status. The trial will continue until 75 deaths have been recorded.

Phase 2, Randomized, Double-Blind, Placebo-Controlled of the Efficacy and Safety of CF102 in Hepatocellular Carcinoma (HCC)

A Phase 2 Study in the Second-Line Treatment of Advanced Hepatocellular Carcinoma in Subjects With Child-Pugh Class B Cirrhosis

Evaluate the efficacy of orally administered CF102 25 mg twice daily (BID) as compared to placebo, as determined by Overall Survival (OS), when used as second-line therapy in subjects with advanced hepatocellular carcinoma (HCC) and Child-Pugh Class B (CPB) cirrhosis. Overall Survival is defined as the time from Baseline (Cycle 1 Day 1) to death due to any cause, calculated as (date of death- date of Cycle 1 Day 1) +1.OS will be summarized in months, which will be obtained by dividing OS in days by 30 days/month. Summary statistics will be determined using the Kaplan-Meier (KM) estimate of the survival function and the between-treatment comparison will be performed using the logrank test as the primary analysis.

Time to Progression (TTP) is the time from Baseline to the first Overall Response of Progressive Disease (PD), calculated as date of first PD - date of Cycle 1 Day 1+1. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. TTP will be summarized in months, which will be obtained by dividing TTP in days by 30 days/month. Summary statistics will be determined using the KM estimate of the survival function for TTP. The between-treatment comparison will be performed using the logrank test.

Time to Progression-Free Survival (PFS) is the time from Baseline to the first Overall Response of Progressive Disease (PD) or death due to any cause if the subject dies without experiencing PD, calculated as date of first PD or date of death - date of Cycle 1 Day 1+1. PFS will be summarized in months, which will be obtained by dividing PFS in days by 30 days/month. Summary statistics will be determined using the KM estimate of the survival function for PFS. The between-treatment comparison will be performed using the logrank test.

Objective Response Rate (ORR) is assessed as the percentage of subjects who achieved a Complete Response (CR) or Partial Response (PR). Per RECIST criteria v1.1, CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm; PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response is the sum of subjects achieving CR or PR.

Disease Control Rate (DCR) is assessed as the percentage of subjects who achieved a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) using RECIST criteria. Per RECIST criteria v1.1, CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm; PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm) taking as reference the smallest sum diameters while on study.

The raw and change from baseline (CFB) for each laboratory parameter (alanine aminotransferase (ALT), albumin, aspartate aminotransferase (AST), bilirubin (direct and total), International Normalized Ratio (INR),and prothrombin time (PT)) will be summarized by treatment and visit. CFB is calculated as (Value at Post-Baseline visit - Value at Baseline). The baseline value used in the calculations of CFB is the value taken at Cycle 1 Day 1.

Summary statistics for WBC adenosine A3 receptor (A3AR) expression and CFB in WBC A3AR expression will be provided by treatment and visit. A3AR mRNA expression in WBC was determined from blood collected to a PAXgene RNA tubes (Qiagen, Venlo, The Netherlands), using the QuantiGene Plex 2.0® assay (Thermo Fisher, Waltham, MA, USA). β-actin was used as a reference control, and the oligonucleotide probe sets were designed by Thermo Fisher. Luminescence from each specific probe set was captured by Glomax Multi (Promega, Madison, WI, USA). A3AR was expressed in units, where 1 unit was defined as the mean of A3AR expression in healthy subjects (n = 50). Healthy subjects were 20-70 years of age with no known illness and no prior treatment.

Describe the PK parameter CL/F (L/h) of namodenoson in subjects with Child-Pugh Class B cirrhosis who received twice daily administration of namodenoson for 29 days in Study CF102-201HCC at Day 1 and Day 29. In order to use a model-based Bayesian analysis in these subjects, a population PK (PPK) model of namodenoson had to be first created with the rich namodenoson concentration data available from two previously conducted studies (healthy volunteers in CF102-101 receiving single doses of 1 to 40 mg; and advanced hepatocellular carcinoma patients in CF102-102HCC receiving 1 to 25 mg BID of namodenoson for 29 days).

Describe the PK parameter Vc/F (L) of namodenoson in subjects with Child-Pugh Class B cirrhosis who received twice daily administration of namodenoson for 29 days in Study CF102-201HCC at Day 1 and Day 29. In order to use a model-based Bayesian analysis in these subjects, a population PK (PPK) model of namodenoson had to be first created with the rich namodenoson concentration data available from two previously conducted studies (healthy volunteers in CF102-101 receiving single doses of 1 to 40 mg; and advanced hepatocellular carcinoma patients in CF102-102HCC receiving 1 to 25 mg BID of namodenoson for 29 days).

Describe the PK parameter Vp/F (L) of namodenoson in subjects with Child-Pugh Class B cirrhosis who received twice daily administration of namodenoson for 29 days in Study CF102-201HCC at Day 1 and Day 29. In order to use a model-based Bayesian analysis in these subjects, a population PK (PPK) model of namodenoson had to be first created with the rich namodenoson concentration data available from two previously conducted studies (healthy volunteers in CF102-101 receiving single doses of 1 to 40 mg; and advanced hepatocellular carcinoma patients in CF102-102HCC receiving 1 to 25 mg BID of namodenoson for 29 days).

Describe the PK parameter Vss/F (L) of namodenoson in subjects with Child-Pugh Class B cirrhosis who received twice daily administration of namodenoson for 29 days in Study CF102-201HCC at Day 1 and Day 29. In order to use a model-based Bayesian analysis in these subjects, a population PK (PPK) model of namodenoson had to be first created with the rich namodenoson concentration data available from two previously conducted studies (healthy volunteers in CF102-101 receiving single doses of 1 to 40 mg; and advanced hepatocellular carcinoma patients in CF102-102HCC receiving 1 to 25 mg BID of namodenoson for 29 days).

Describe the PK parameter Elimination half-life (hours) of namodenoson in subjects with Child-Pugh Class B cirrhosis who received twice daily administration of namodenoson for 29 days in Study CF102-201HCC at Day 1 and Day 29. In order to use a model-based Bayesian analysis in these subjects, a population PK (PPK) model of namodenoson had to be first created with the rich namodenoson concentration data available from two previously conducted studies (healthy volunteers in CF102-101 receiving single doses of 1 to 40 mg; and advanced hepatocellular carcinoma patients in CF102-102HCC receiving 1 to 25 mg BID of namodenoson for 29 days).

Describe the PK parameter AUC_0-12, steady state (ng\*h/mL) of namodenoson in subjects with Child-Pugh Class B cirrhosis who received twice daily administration of namodenoson for 29 days in Study CF102-201HCC at Day 1 and Day 29. In order to use a model-based Bayesian analysis in these subjects, a population PK (PPK) model of namodenoson had to be first created with the rich namodenoson concentration data available from two previously conducted studies (healthy volunteers in CF102-101 receiving single doses of 1 to 40 mg; and advanced hepatocellular carcinoma patients in CF102-102HCC receiving 1 to 25 mg BID of namodenoson for 29 days).

Serious adverse event classification based on the FDA regulatory definition of a serious AE.

CF102 25 mg capsules administered orally BID

Placebo Tablets of CF102

Total

Age, Continuous

White/Caucasian

Black/African

Oriental

Other

Race/Ethnicity, Customized

Diagnostic Procedure

Pnina Fishman, PhD, CEO

The between-treatment comparison (CF102 vs Placebo) of Overall Survival will be performed using the log rank test as the primary analysis.

12-month Survival - Yes

12-month Survival - No

The analysis of the primary outcome measure was performed on the Intent-To-Treat (ITT) Population, defined as all subjects who received at least one dose of study medication (i.e., Safety Population) with any post-Baseline assessment recorded. Exclusion of subjects from the ITT Population was determined prior to unblinding.

Number of Subjects With Overall Survival

The between-treatment comparison (CF102 vs Placebo) of Time to Progression will be performed using the log rank test as the primary analysis.

The analysis of the secondary outcome measure was performed on the Intent-To-Treat (ITT) Population, defined as all subjects who received at least one dose of study medication (i.e., Safety Population) with any post-Baseline assessment recorded. Exclusion of subjects from the ITT Population was determined prior to unblinding.

Time to Progression (TTP)

The between-treatment comparison (CF102 vs Placebo) will be performed on Time to Progression Free Survival using the logrank test.

Time to Progression-Free Survival (PFS)

Cycle 3 Day 1

Cycle 5 Day 1

Cycle 7 Day 1

Cycle 9 Day 1

Cycle 11 Day 1

Objective Response Rate (ORR)

Disease Control Rate (DCR)

Between-treatment comparisons of ALT will be performed at Cycle 11 Day 15 using ANCOVA with CFB as the dependent variable and the Baseline value of the variable as the covariate.

Between-treatment comparisons of AST will be performed at Cycle 11 Day 15 using ANCOVA with CFB as the dependent variable and the Baseline value of the variable as the covariate.

Between-treatment comparisons of Albumin will be performed at Cycle 11 Day 15 using ANCOVA with CFB as the dependent variable and the Baseline value of the variable as the covariate.

Between-treatment comparisons of Bilirubin (direct) will be performed at Cycle 11 Day 15 using ANCOVA with CFB as the dependent variable and the Baseline value of the variable as the covariate.

Between-treatment comparisons of Bilirubin (Total) will be performed at Cycle 11 Day 15 using ANCOVA with CFB as the dependent variable and the Baseline value of the variable as the covariate.

Between-treatment comparisons of PT will be performed at Cycle 11 Day 15 using ANCOVA with CFB as the dependent variable and the Baseline value of the variable as the covariate.

Between-treatment comparisons of INR will be performed at Cycle 11 Day 15 using ANCOVA with CFB as the dependent variable and the Baseline value of the variable as the covariate.

ALT - Pre-Study

ALT - Cycle 1 Day 1

ALT - Cycle 11 Day 15

ALT - CFB to Cycle 11 Day 15

AST - Pre-Study

AST - Cycle 1 Day 1

AST - Cycle 11 Day 15

AST - CFB to Cycle 11 Day 15

Albumin - Pre-Study

Albumin - Cycle 1 Day 1

Albumin - Cycle 11 Day 15

Albumin - CFB to Cycle 11 Day 15

Bilirubin (Direct) - Pre-Study

Bilirubin (Direct) - Cycle 1 Day 1

Bilirubin (Direct) - Cycle 11 Day 15

Bilirubin (Direct) - CFB to Cycle 11 Day 15

Bilirubin (Total) - Pre-Study

Bilirubin (Total) - Cycle 1 Day 1

Bilirubin (Total) - Cycle 11 Day 15

Bilirubin (Total) - CFB to Cycle 11 Day 15

Prothrombin Time (PT) - Pre-Study

PT - Cycle 1 Day 1

PT - Cycle 11 Day 15

PT - CFB to Cycle 11 Day 15

International Normalized Ratio (INR) - Pre-Study

INR - Cycle 1 Day 1

INR - Cycle 11 Day 15

INR - CFB to Cycle 11 Day 15

Summary Statistics of Laboratory Parameters Associated With Viral Hepatitis, Hepatic Dysfunction, and Cirrhosis

Baseline - Cycle 1 Day 1

CFB to Cycle 11 Day 1

The analysis of the secondary outcome measure was performed using data from selected study sites on subjects in the Intent-To-Treat (ITT) Population, defined as all subjects who received at least one dose of study medication (i.e., Safety Population) with any post-Baseline assessment recorded. Exclusion of subjects from the ITT Population was determined prior to unblinding. The selection of study sites for participation in the A3AR blood sampling was determined according to the protocol.

Summary Statistics of White Blood Cell (WBC) Adenosine A3 Receptor (A3AR) Expression and Clinical Response - WBC Adenosine A3 Receptor (A3AR) Expression

The PK analysis was conducted on advanced hepatocellular carcinoma patients with Child Pugh class B cirrhosis who received 25 mg BID for 29 days.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1-2 Study of CF102 in Patients With Advanced Hepatocellular Carcinoma	NCT00790218	Hepatocellular ...	CF102	18 Years - 80 Years	Can-Fite BioPharma
Phase 2, Randomized, Double-Blind, Placebo-Controlled of the Efficacy and Safety of CF102 in Hepatocellular Carcinoma (HCC)	NCT02128958	Hepatocellular ...	CF102 Placebo	18 Years -	Can-Fite BioPharma
Phase 2, Randomized, Double-Blind, Placebo-Controlled of the Efficacy and Safety of CF102 in Hepatocellular Carcinoma (HCC)	NCT02128958	Hepatocellular ...	CF102 Placebo	18 Years -	Can-Fite BioPharma

Spots Global Cancer Trial Database for cf102

Every month we try and update this database with for cf102 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cf102

Every month we try and update this database with for cf102 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cf102 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.