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

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ClinicalTrials.gov Identifier: NCT02128958
Recruitment Status : Completed
First Posted : May 1, 2014
Results First Posted : December 29, 2021
Last Update Posted : October 4, 2022
Sponsor:
Information provided by (Responsible Party):
Can-Fite BioPharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Hepatocellular Carcinoma
Interventions Drug: CF102
Drug: Placebo
Enrollment 78
Recruitment Details  
Pre-assignment Details  
Arm/Group Title CF102 Placebo Tablets of CF102
Hide Arm/Group Description CF102 25 mg capsules administered orally BID Placebo capsules administered orally BID
Period Title: Overall Study
Started 50 28
Completed 29 18
Not Completed 21 10
Arm/Group Title CF102 Placebo Tablets of CF102 Total
Hide Arm/Group Description CF102 25 mg capsules administered orally BID Placebo capsules administered orally BID Total of all reporting groups
Overall Number of Baseline Participants 50 28 78
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants 28 participants 78 participants
62.4  (11.64) 65.2  (10.22) 63.4  (11.17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 28 participants 78 participants
Female
12
  24.0%
9
  32.1%
21
  26.9%
Male
38
  76.0%
19
  67.9%
57
  73.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 28 participants 78 participants
White/Caucasian
48
  96.0%
27
  96.4%
75
  96.2%
Black/African
1
   2.0%
0
   0.0%
1
   1.3%
Oriental
0
   0.0%
1
   3.6%
1
   1.3%
Other
1
   2.0%
0
   0.0%
1
   1.3%
Diagnostic Procedure  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 28 participants 78 participants
Cytology/Histology
27
  54.0%
17
  60.7%
44
  56.4%
American Association for the Study of Liver Diseases
23
  46.0%
11
  39.3%
34
  43.6%
1.Primary Outcome
Title Number of Subjects With Overall Survival
Hide Description 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 Frame From date of first treatment (Cycle 1 Day 1) until date of death from any cause, assessed up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CF102 Placebo Tablets of CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Placebo capsules administered orally BID
Overall Number of Participants Analyzed 50 28
Measure Type: Count of Participants
Unit of Measure: Participants
12-month Survival - Yes
16
  32.0%
4
  14.3%
12-month Survival - No
34
  68.0%
24
  85.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments The between-treatment comparison (CF102 vs Placebo) of Overall Survival will be performed using the log rank test as the primary analysis.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.536
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Time to Progression (TTP)
Hide Description 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 Frame From date of first treatment (Cycle 1 Day 1) until the date of first documented progression, assessed up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CF102 Placebo Tablets of CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Placebo capsules administered orally BID
Overall Number of Participants Analyzed 50 28
Median (Inter-Quartile Range)
Unit of Measure: Months
5.1
(1.9 to 11.2)
3.3
(1.9 to 33.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments The between-treatment comparison (CF102 vs Placebo) of Time to Progression will be performed using the log rank test as the primary analysis.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .371
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Time to Progression-Free Survival (PFS)
Hide Description 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.
Time Frame From date of first treatment (Cycle 1 Day 1) until the date of first documented disease progression or date of death, which occurred first, assessed up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CF102 Placebo Tablets of CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Placebo capsules administered orally BID
Overall Number of Participants Analyzed 50 28
Median (Inter-Quartile Range)
Unit of Measure: months
2.5
(1.8 to 6.1)
1.9
(1.8 to 3.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments The between-treatment comparison (CF102 vs Placebo) will be performed on Time to Progression Free Survival using the logrank test.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.521
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description 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.
Time Frame The end of even-numbered cycles (Cycle 3 Day 1,Cycle 5 Day 1,Cycle 7 Day 1, Cycle 9 Day 1, Cycle 11 Day 1) assessed up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CF102 Placebo Tablets of CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Placebo capsules administered orally BID
Overall Number of Participants Analyzed 50 28
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 3 Day 1
1
   2.0%
0
   0.0%
Cycle 5 Day 1
2
   4.0%
0
   0.0%
Cycle 7 Day 1
2
   4.0%
0
   0.0%
Cycle 9 Day 1
2
   4.0%
0
   0.0%
Cycle 11 Day 1
2
   4.0%
0
   0.0%
5.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description 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.
Time Frame The end of even-numbered cycles (Cycle 3 Day 1,Cycle 5 Day 1,Cycle 7 Day 1, Cycle 9 Day 1, Cycle 11 Day 1) assessed up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CF102 Placebo Tablets of CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Placebo capsules administered orally BID
Overall Number of Participants Analyzed 50 28
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 3 Day 1
19
  38.0%
10
  35.7%
Cycle 5 Day 1
9
  18.0%
2
   7.1%
Cycle 7 Day 1
7
  14.0%
2
   7.1%
Cycle 9 Day 1
5
  10.0%
2
   7.1%
Cycle 11 Day 1
4
   8.0%
1
   3.6%
6.Secondary Outcome
Title Summary Statistics of Laboratory Parameters Associated With Viral Hepatitis, Hepatic Dysfunction, and Cirrhosis
Hide Description 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.
Time Frame Baseline (Cycle 1 Day 1); Cycle 11 Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CF102 Placebo Tablets of CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Placebo capsules administered orally BID
Overall Number of Participants Analyzed 50 28
Mean (Standard Deviation)
Unit of Measure: U/L
ALT - Pre-Study Number Analyzed 49 participants 28 participants
47.4  (29.97) 36.3  (20.93)
ALT - Cycle 1 Day 1 Number Analyzed 50 participants 28 participants
46.5  (25.60) 35.7  (26.75)
ALT - Cycle 11 Day 15 Number Analyzed 11 participants 4 participants
55.0  (45.39) 44.0  (45.23)
ALT - CFB to Cycle 11 Day 15 Number Analyzed 11 participants 4 participants
7.2  (43.73) 10.0  (23.17)
AST - Pre-Study Number Analyzed 49 participants 28 participants
83.8  (50.36) 64.5  (38.49)
AST - Cycle 1 Day 1 Number Analyzed 50 participants 28 participants
88.8  (58.88) 66.7  (40.84)
AST - Cycle 11 Day 15 Number Analyzed 11 participants 4 participants
77.1  (57.5) 46.5  (23.90)
AST - CFB to Cycle 11 Day 15 Number Analyzed 11 participants 4 participants
7.4  (46.34) 8.3  (23.21)
Albumin - Pre-Study Number Analyzed 49 participants 28 participants
32.8  (4.97) 33.7  (5.44)
Albumin - Cycle 1 Day 1 Number Analyzed 50 participants 28 participants
32.4  (5.21) 32.9  (5.50)
Albumin - Cycle 11 Day 15 Number Analyzed 11 participants 4 participants
36.5  (3.88) 35.8  (4.27)
Albumin - CFB to Cycle 11 Day 15 Number Analyzed 11 participants 4 participants
2.2  (5.17) -0.8  (8.85)
Bilirubin (Direct) - Pre-Study Number Analyzed 49 participants 27 participants
9.0  (7.33) 5.4  (3.32)
Bilirubin (Direct) - Cycle 1 Day 1 Number Analyzed 50 participants 27 participants
9.6  (9.00) 5.3  (3.71)
Bilirubin (Direct) - Cycle 11 Day 15 Number Analyzed 10 participants 4 participants
4.2  (2.39) 3.3  (0.96)
Bilirubin (Direct) - CFB to Cycle 11 Day 15 Number Analyzed 10 participants 4 participants
-0.7  (3.16) 1.3  (2.5)
Bilirubin (Total) - Pre-Study Number Analyzed 49 participants 28 participants
20.5  (12.9) 14.9  (6.39)
Bilirubin (Total) - Cycle 1 Day 1 Number Analyzed 50 participants 28 participants
21.1  (15.94) 15.1  (9.62)
Bilirubin (Total) - Cycle 11 Day 15 Number Analyzed 11 participants 4 participants
14.3  (4.10) 9.8  (2.87)
Bilirubin (Total) - CFB to Cycle 11 Day 15 Number Analyzed 11 participants 4 participants
0.7  (5.41) 2.0  (3.56)
Prothrombin Time (PT) - Pre-Study Number Analyzed 46 participants 28 participants
12.39  (1.85) 12.08  (1.097)
PT - Cycle 1 Day 1 Number Analyzed 50 participants 28 participants
12.17  (1.37) 12.30  (1.33)
PT - Cycle 11 Day 15 Number Analyzed 9 participants 4 participants
11.82  (1.128) 11.70  (0.942)
PT - CFB to Cycle 11 Day 15 Number Analyzed 9 participants 4 participants
0.08  (0.657) 0.53  (1.212)
International Normalized Ratio (INR) - Pre-Study Number Analyzed 46 participants 28 participants
1.19  (0.176) 1.15  (0.114)
INR - Cycle 1 Day 1 Number Analyzed 50 participants 28 participants
1.17  (0.141) 1.19  (0.138)
INR - Cycle 11 Day 15 Number Analyzed 9 participants 4 participants
1.11  (0.105) 1.13  (0.096)
INR - CFB to Cycle 11 Day 15 Number Analyzed 9 participants 4 participants
-0.01  (0.078) 0.05  (0.129)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments 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.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.988
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments 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.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.989
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments 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.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.717
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments 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.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.891
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments 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.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.275
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments 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.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.549
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection CF102, Placebo Tablets of CF102
Comments 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.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.479
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Summary Statistics of White Blood Cell (WBC) Adenosine A3 Receptor (A3AR) Expression and Clinical Response - WBC Adenosine A3 Receptor (A3AR) Expression
Hide Description 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.
Time Frame Baseline (Cycle 1 Day 1) and Cycle 11 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CF102 Placebo Tablets of CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Placebo capsules administered orally BID
Overall Number of Participants Analyzed 32 20
Mean (Standard Deviation)
Unit of Measure: ratio of patient to healthy control
Baseline - Cycle 1 Day 1 Number Analyzed 32 participants 20 participants
1.789  (2.2103) 2.339  (3.2906)
Cycle 11 Day 1 Number Analyzed 9 participants 2 participants
2.821  (3.8114) 1.1  (0.0849)
CFB to Cycle 11 Day 1 Number Analyzed 9 participants 2 participants
0.757  (0.7948) -0.3  (0.5798)
8.Secondary Outcome
Title Pharmacokinetics (PK) Parameters of CF102 - CL/F (L/h)
Hide Description 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).
Time Frame Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted on advanced hepatocellular carcinoma patients with Child Pugh class B cirrhosis who received 25 mg BID for 29 days.
Arm/Group Title CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Overall Number of Participants Analyzed 45
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
12.42
(57.83%)
9.Secondary Outcome
Title Pharmacokinetics (PK) Parameters of CF102 - Vc/F (L)
Hide Description 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).
Time Frame Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted on advanced hepatocellular carcinoma patients with Child Pugh class B cirrhosis who received 25 mg BID for 29 days.
Arm/Group Title CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Overall Number of Participants Analyzed 45
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
254.20
(54.56%)
10.Secondary Outcome
Title Pharmacokinetics (PK) Parameters of CF102 - Vp/F (L)
Hide Description 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).
Time Frame Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted on advanced hepatocellular carcinoma patients with Child Pugh class B cirrhosis who received 25 mg BID for 29 days.
Arm/Group Title CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Overall Number of Participants Analyzed 45
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
49.99
(16.33%)
11.Secondary Outcome
Title Pharmacokinetics (PK) Parameters of CF102 - Vss/F (L)
Hide Description 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).
Time Frame Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted on advanced hepatocellular carcinoma patients with Child Pugh class B cirrhosis who received 25 mg BID for 29 days.
Arm/Group Title CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Overall Number of Participants Analyzed 45
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
309.56
(44.31%)
12.Secondary Outcome
Title Pharmacokinetics (PK) Parameters of CF102 - Elimination Half-life (Hours)
Hide Description 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).
Time Frame Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted on advanced hepatocellular carcinoma patients with Child Pugh class B cirrhosis who received 25 mg BID for 29 days.
Arm/Group Title CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Overall Number of Participants Analyzed 45
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
18.39
(29.93%)
13.Secondary Outcome
Title Pharmacokinetics (PK) Parameters of CF102 - AUC_0-12, Steady State (ng*h/mL)
Hide Description 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).
Time Frame Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted on advanced hepatocellular carcinoma patients with Child Pugh class B cirrhosis who received 25 mg BID for 29 days.
Arm/Group Title CF102
Hide Arm/Group Description:
CF102 25 mg capsules administered orally BID
Overall Number of Participants Analyzed 45
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
2012.54
(57.83%)
Time Frame AEs were recorded for each subject at the start of Cycle 1 Day 1 visit and followed to the 28-day Follow-Up Visit (28 days post End of Dosing) for up to 1 year/ Open-Label (OL) Follow-Up Visit (28 days post OL End of Dosing) for an average of 1 year. For observed toxicity thought to be at least possibly related to study drug was not resolved by the 28-day Follow-Up Visit/OL Follow-Up Visit, the subject was followed until the event resolved or stabilized, for an average of up to 24 months.
Adverse Event Reporting Description Serious adverse event classification based on the FDA regulatory definition of a serious AE.
 
Arm/Group Title CF102 Placebo Tablets of CF102
Hide Arm/Group Description CF102 25 mg capsules administered orally BID Placebo capsules administered orally BID
All-Cause Mortality
CF102 Placebo Tablets of CF102
Affected / at Risk (%) Affected / at Risk (%)
Total   34/50 (68.00%)   24/28 (85.71%) 
Hide Serious Adverse Events
CF102 Placebo Tablets of CF102
Affected / at Risk (%) Affected / at Risk (%)
Total   37/50 (74.00%)   20/28 (71.43%) 
Blood and lymphatic system disorders     
Anaemia  1  0/50 (0.00%)  1/28 (3.57%) 
Cardiac disorders     
Cardiac failure  1  1/50 (2.00%)  0/28 (0.00%) 
Myocardial infarction  1  0/50 (0.00%)  1/28 (3.57%) 
Cardio-respiratory arrest  1  2/50 (4.00%)  1/28 (3.57%) 
Gastrointestinal disorders     
Subileus  1  1/50 (2.00%)  0/28 (0.00%) 
Abdominal adhesions  1  1/50 (2.00%)  0/28 (0.00%) 
Gastrointestinal haemorrhage  1  4/50 (8.00%)  0/28 (0.00%) 
Ascites  1  2/50 (4.00%)  1/28 (3.57%) 
Peritoneal haemorrhage  1  1/50 (2.00%)  0/28 (0.00%) 
Oesophageal varices haemorrhage  1  0/50 (0.00%)  1/28 (3.57%) 
Abdominal Pain  1  1/50 (2.00%)  0/28 (0.00%) 
General disorders     
Multiple organ dysfunction syndrome  1  0/50 (0.00%)  1/28 (3.57%) 
Death  1  1/50 (2.00%)  0/28 (0.00%) 
Disease Progression  1  13/50 (26.00%)  5/28 (17.86%) 
Chest pain  1  0/50 (0.00%)  1/28 (3.57%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  1  1/50 (2.00%)  0/28 (0.00%) 
Hepatic failure  1  0/50 (0.00%)  2/28 (7.14%) 
Hepatic cirrhosis  1  1/50 (2.00%)  0/28 (0.00%) 
Infections and infestations     
Bronchitis  1  0/50 (0.00%)  1/28 (3.57%) 
Cellulitis  1  1/50 (2.00%)  0/28 (0.00%) 
Sepsis  1  1/50 (2.00%)  0/28 (0.00%) 
Investigations     
Hepatic enzyme increased/  1  1/50 (2.00%)  0/28 (0.00%) 
Aspartate aminotransferase increased  1  1/50 (2.00%)  0/28 (0.00%) 
Bilirubin conjugated increased  1  0/50 (0.00%)  1/28 (3.57%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  1/50 (2.00%)  0/28 (0.00%) 
Hyponatraemia  1  1/50 (2.00%)  0/28 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatocellular carcinoma  1  5/50 (10.00%)  2/28 (7.14%) 
Malignant neoplasm progression/  1  1/50 (2.00%)  1/28 (3.57%) 
Metastases to lung  1  0/50 (0.00%)  1/28 (3.57%) 
Nervous system disorders     
Coma  1  0/50 (0.00%)  1/28 (3.57%) 
Encephalopathy  1  1/50 (2.00%)  0/28 (0.00%) 
Hepatic Encephalopathy  1  3/50 (6.00%)  1/28 (3.57%) 
Ischaemic stroke  1  1/50 (2.00%)  0/28 (0.00%) 
Renal and urinary disorders     
Renal failure  1  0/50 (0.00%)  1/28 (3.57%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  0/50 (0.00%)  1/28 (3.57%) 
Dyspnoea  1  0/50 (0.00%)  1/28 (3.57%) 
Acute respiratory failure  1  1/50 (2.00%)  0/28 (0.00%) 
Pleural effusion  1  1/50 (2.00%)  1/28 (3.57%) 
Vascular disorders     
Vena cava thrombosis  1  1/50 (2.00%)  0/28 (0.00%) 
Subclavian vein thrombosis  1  0/50 (0.00%)  1/28 (3.57%) 
Superior vena cava occlusion  1  0/50 (0.00%)  1/28 (3.57%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CF102 Placebo Tablets of CF102
Affected / at Risk (%) Affected / at Risk (%)
Total   46/50 (92.00%)   26/28 (92.86%) 
Blood and lymphatic system disorders     
Anaemia  1  8/50 (16.00%)  5/28 (17.86%) 
Gastrointestinal disorders     
Abdominal Pain  1  9/50 (18.00%)  3/28 (10.71%) 
Ascites  1  10/50 (20.00%)  2/28 (7.14%) 
Constipation  1  0/50 (0.00%)  2/28 (7.14%) 
Diarrhoea  1  2/50 (4.00%)  2/28 (7.14%) 
Gastrointestinal haemorrhage  1  4/50 (8.00%)  0/28 (0.00%) 
Nausea  1  9/50 (18.00%)  6/28 (21.43%) 
Vomiting  1  3/50 (6.00%)  4/28 (14.29%) 
General disorders     
Asthenia  1  7/50 (14.00%)  6/28 (21.43%) 
Chest pain  1  2/50 (4.00%)  3/28 (10.71%) 
Disease Progression  1  14/50 (28.00%)  5/28 (17.86%) 
Fatigue  1  9/50 (18.00%)  3/28 (10.71%) 
Oedema peripheral  1  10/50 (20.00%)  5/28 (17.86%) 
Pain  1  2/50 (4.00%)  2/28 (7.14%) 
Pyrexia  1  3/50 (6.00%)  2/28 (7.14%) 
Hepatobiliary disorders     
Hepatic failure  1  0/50 (0.00%)  2/28 (7.14%) 
Hyperbilirubinaemia  1  4/50 (8.00%)  0/28 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  2/50 (4.00%)  2/28 (7.14%) 
Aspartate aminotransferase increased  1  6/50 (12.00%)  2/28 (7.14%) 
Blood alkaline phosphatase increased  1  0/50 (0.00%)  2/28 (7.14%) 
Blood bilirubin increased  1  0/50 (0.00%)  3/28 (10.71%) 
Blood thyroid stimulating hormone increased  1  1/50 (2.00%)  3/28 (10.71%) 
Tri-iodothyronine free decreased  1  0/50 (0.00%)  2/28 (7.14%) 
Weight decreased  1  4/50 (8.00%)  4/28 (14.29%) 
Weight increased  1  4/50 (8.00%)  3/28 (10.71%) 
Metabolism and nutrition disorders     
Decreased appetite  1  4/50 (8.00%)  1/28 (3.57%) 
Hyperkalaemia  1  2/50 (4.00%)  2/28 (7.14%) 
Hypoalbuminaemia  1  4/50 (8.00%)  2/28 (7.14%) 
Hypoglycaemia  1  3/50 (6.00%)  0/28 (0.00%) 
Hyponatraemia  1  2/50 (4.00%)  3/28 (10.71%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  3/50 (6.00%)  1/28 (3.57%) 
Pain in extremity  1  1/50 (2.00%)  3/28 (10.71%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatocellular carcinoma  1  5/50 (10.00%)  2/28 (7.14%) 
Nervous system disorders     
Dizziness  1  3/50 (6.00%)  2/28 (7.14%) 
Headache  1  3/50 (6.00%)  1/28 (3.57%) 
Hepatic encephalopathy  1  3/50 (6.00%)  1/28 (3.57%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/50 (8.00%)  3/28 (10.71%) 
Dyspnoea  1  3/50 (6.00%)  2/28 (7.14%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pnina Fishman, PhD, CEO
Organization: Can-Fite BioPharma
Phone: 972-3-924-1114
EMail: pnina@canfite.co.il
Layout table for additonal information
Responsible Party: Can-Fite BioPharma
ClinicalTrials.gov Identifier: NCT02128958    
Other Study ID Numbers: CF102-201HCC
First Submitted: April 27, 2014
First Posted: May 1, 2014
Results First Submitted: August 4, 2021
Results First Posted: December 29, 2021
Last Update Posted: October 4, 2022