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

Primary Purpose

Hepatocellular Carcinoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CF102
Placebo
Sponsored by
Can-Fite BioPharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma, Child-Pugh Class B Cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

    • For subjects without underlying cirrhosis at the time of diagnosis, diagnosis of HCC documented by cytology and/or histology.
    • For subjects 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 (Appendix E).
  3. HCC is advanced, ie, treatment-refractory or metastatic, and no standard therapies are expected to be curative.
  4. Receipt of 1 previous systemic drug therapy for at least 3 weeks and withdrawal from treatment due either to intolerability or to radiographic disease progression. If treatment was withdrawn due to intolerability manifested as a Grade 3 or 4 event by National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE v4.0), less than 3 weeks of continuous prior administration prior to withdrawal is acceptable (see also Exclusion Criterion #3).
  5. Prior systemic treatment was discontinued for at least 2 weeks prior to the Baseline Visit.
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2 (Appendix B).
  7. Cirrhosis classified as Child-Pugh Class B (Appendix C).
  8. The following laboratory values must be documented within 3 days prior to the first dose of study drug:

    • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
    • Platelet count ≥ 75 × 109/L
    • Serum creatinine ≤ 2.0 mg/dL
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × the upper limit of normal (ULN)
    • Total bilirubin ≤ 3.0 mg/dL
    • Serum albumin ≥ 2.8 g/dL
    • Prothrombin time (PT) no greater than 6 seconds longer than control.
  9. Life expectancy of ≥ 6 weeks.

Exclusion Criteria:

  1. Receipt of no, or of >1, prior systemic drug therapies for HCC.
  2. 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.
  3. Presence of an acute or chronic toxicity of prior chemotherapy that has not resolved to ≤ Grade 1, as determined by CTCAE v 4.0.
  4. Locoregional treatment within 4 weeks prior to the Baseline Visit.
  5. Major surgery or radiation therapy within 4 weeks prior to the Baseline Visit.
  6. Use of any investigational agent within 4 weeks prior to the Baseline Visit.
  7. Child-Pugh Class A or C cirrhosis, or hepatic encephalopathy.
  8. Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusion within 4 weeks prior to the Baseline Visit.
  9. Active bacterial, viral, or fungal infection requiring systemic therapy or operative or radiological intervention.
  10. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness.
  11. Liver transplant.
  12. Active malignancy other than HCC.
  13. Uncontrolled arterial hypertension or congestive heart failure (New York Heart Association Classification 3 or 4) (Appendix B).
  14. 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.
  15. History of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to > 450 msec for males or > 470 msec for females.
  16. Pregnant or lactating female.
  17. 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 subject inappropriate for entry into this trial.

Sites / Locations

  • University of Colorado Cancer Center
  • Simmons Cancer Center
  • Complex Oncology Center - Plovdiv
  • Multiprofile Hospital for Active Treatment Central Onco Hospita
  • Multiprofile Hospital for Active Treatment "Tokuda Hospital Sofia" AD
  • Multiprofile Hospital for Active Treatment for women's health - Nadezhda
  • Multiprofile Hospital for Active Treatment Serdica
  • Multiprofile Hospital for Active Treatment "Sveta Marina" EAD
  • Rabin Medical Center
  • Institutul Clinic Fundeni - Sectia Oncologie Medicala
  • Clinica Bendis - Oncologie Medicala
  • Centrul de Oncologie ONCOLAB
  • Institutul Regional de Oncologie Iasi - Sectia Oncologie Medicala
  • Spitalul Pelican Impex SRL- Sectia Oncologie Medicala
  • SC DACMED SRL - Oncologie
  • Spitalului Clinic Judetean de Urgenta - Sectia Oncologie Medicala
  • Spitalul Judetean de Urgenta "Sf. Ioan Cel Nou" - sectia Oncologie Medicala
  • Vojnomedicinska Akademija Beograd
  • Zdravstveni Centar Kladovo Služba Onkologije
  • Klinički Centar Niš Klinika za Onkologiju
  • Institut za Onkologiju Vojvodine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CF102

Placebo tablets of CF102

Arm Description

orally q12h

orally q12h

Outcomes

Primary Outcome Measures

Number of Subjects With Overall Survival
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.

Secondary Outcome Measures

Time to Progression (TTP)
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)
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)
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)
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.
Summary Statistics of Laboratory Parameters Associated With Viral Hepatitis, Hepatic Dysfunction, and Cirrhosis
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 of White Blood Cell (WBC) Adenosine A3 Receptor (A3AR) Expression and Clinical Response - WBC Adenosine A3 Receptor (A3AR) Expression
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.
Pharmacokinetics (PK) Parameters of CF102 - CL/F (L/h)
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).
Pharmacokinetics (PK) Parameters of CF102 - Vc/F (L)
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).
Pharmacokinetics (PK) Parameters of CF102 - Vp/F (L)
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).
Pharmacokinetics (PK) Parameters of CF102 - Vss/F (L)
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).
Pharmacokinetics (PK) Parameters of CF102 - Elimination Half-life (Hours)
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).
Pharmacokinetics (PK) Parameters of CF102 - AUC_0-12, Steady State (ng*h/mL)
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).

Full Information

First Posted
April 27, 2014
Last Updated
September 26, 2022
Sponsor
Can-Fite BioPharma
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1. Study Identification

Unique Protocol Identification Number
NCT02128958
Brief Title
Phase 2, Randomized, Double-Blind, Placebo-Controlled of the Efficacy and Safety of CF102 in Hepatocellular Carcinoma (HCC)
Official Title
A Phase 2 Study in the Second-Line Treatment of Advanced Hepatocellular Carcinoma in Subjects With Child-Pugh Class B Cirrhosis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
September 2014 (Actual)
Primary Completion Date
November 27, 2017 (Actual)
Study Completion Date
December 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Can-Fite BioPharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Hepatocellular Carcinoma, Child-Pugh Class B Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
78 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CF102
Arm Type
Experimental
Arm Description
orally q12h
Arm Title
Placebo tablets of CF102
Arm Type
Placebo Comparator
Arm Description
orally q12h
Intervention Type
Drug
Intervention Name(s)
CF102
Other Intervention Name(s)
IB-MECA
Intervention Description
orally q12h
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Inactive pill
Intervention Description
orally q12 hours
Primary Outcome Measure Information:
Title
Number of Subjects With Overall Survival
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
Secondary Outcome Measure Information:
Title
Time to Progression (TTP)
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
Title
Time to Progression-Free Survival (PFS)
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
Title
Objective Response Rate (ORR)
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
Title
Disease Control Rate (DCR)
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
Title
Summary Statistics of Laboratory Parameters Associated With Viral Hepatitis, Hepatic Dysfunction, and Cirrhosis
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
Title
Summary Statistics of White Blood Cell (WBC) Adenosine A3 Receptor (A3AR) Expression and Clinical Response - WBC Adenosine A3 Receptor (A3AR) Expression
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
Title
Pharmacokinetics (PK) Parameters of CF102 - CL/F (L/h)
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
Title
Pharmacokinetics (PK) Parameters of CF102 - Vc/F (L)
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
Title
Pharmacokinetics (PK) Parameters of CF102 - Vp/F (L)
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
Title
Pharmacokinetics (PK) Parameters of CF102 - Vss/F (L)
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
Title
Pharmacokinetics (PK) Parameters of CF102 - Elimination Half-life (Hours)
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
Title
Pharmacokinetics (PK) Parameters of CF102 - AUC_0-12, Steady State (ng*h/mL)
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and females at least 18 years of age. Diagnosis of HCC: For subjects without underlying cirrhosis at the time of diagnosis, diagnosis of HCC documented by cytology and/or histology. For subjects 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 (Appendix E). HCC is advanced, ie, treatment-refractory or metastatic, and no standard therapies are expected to be curative. Receipt of 1 previous systemic drug therapy for at least 3 weeks and withdrawal from treatment due either to intolerability or to radiographic disease progression. If treatment was withdrawn due to intolerability manifested as a Grade 3 or 4 event by National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE v4.0), less than 3 weeks of continuous prior administration prior to withdrawal is acceptable (see also Exclusion Criterion #3). Prior systemic treatment was discontinued for at least 2 weeks prior to the Baseline Visit. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2 (Appendix B). Cirrhosis classified as Child-Pugh Class B (Appendix C). The following laboratory values must be documented within 3 days prior to the first dose of study drug: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L Platelet count ≥ 75 × 109/L Serum creatinine ≤ 2.0 mg/dL Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × the upper limit of normal (ULN) Total bilirubin ≤ 3.0 mg/dL Serum albumin ≥ 2.8 g/dL Prothrombin time (PT) no greater than 6 seconds longer than control. Life expectancy of ≥ 6 weeks. Exclusion Criteria: Receipt of no, or of >1, 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. Presence of an acute or chronic toxicity of prior chemotherapy that has not resolved to ≤ Grade 1, as determined by CTCAE v 4.0. 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. Child-Pugh Class A or C cirrhosis, or hepatic encephalopathy. Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusion within 4 weeks prior to the Baseline Visit. 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) (Appendix B). 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 > 450 msec for males or > 470 msec for females. Pregnant or lactating female. 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 subject inappropriate for entry into this trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael H Silverman
Organizational Affiliation
Can-Fite BioPharma Ltd
Official's Role
Study Director
Facility Information:
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Simmons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Complex Oncology Center - Plovdiv
City
Plovdiv
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment Central Onco Hospita
City
Plovdiv
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment "Tokuda Hospital Sofia" AD
City
Sofia
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment for women's health - Nadezhda
City
Sofia
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment Serdica
City
Sofia
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment "Sveta Marina" EAD
City
Varna
Country
Bulgaria
Facility Name
Rabin Medical Center
City
Petach Tikva
Country
Israel
Facility Name
Institutul Clinic Fundeni - Sectia Oncologie Medicala
City
Bucuresti
Country
Romania
Facility Name
Clinica Bendis - Oncologie Medicala
City
Cluj
Country
Romania
Facility Name
Centrul de Oncologie ONCOLAB
City
Craiova
Country
Romania
Facility Name
Institutul Regional de Oncologie Iasi - Sectia Oncologie Medicala
City
Iaşi
Country
Romania
Facility Name
Spitalul Pelican Impex SRL- Sectia Oncologie Medicala
City
Oradea
Country
Romania
Facility Name
SC DACMED SRL - Oncologie
City
Ploieşti
Country
Romania
Facility Name
Spitalului Clinic Judetean de Urgenta - Sectia Oncologie Medicala
City
Sibiu
Country
Romania
Facility Name
Spitalul Judetean de Urgenta "Sf. Ioan Cel Nou" - sectia Oncologie Medicala
City
Suceava
Country
Romania
Facility Name
Vojnomedicinska Akademija Beograd
City
Belgrade
Country
Serbia
Facility Name
Zdravstveni Centar Kladovo Služba Onkologije
City
Kladovo
Country
Serbia
Facility Name
Klinički Centar Niš Klinika za Onkologiju
City
Niš
Country
Serbia
Facility Name
Institut za Onkologiju Vojvodine
City
Sremska Kamenica
Country
Serbia

12. IPD Sharing Statement

Citations:
PubMed Identifier
33430312
Citation
Stemmer SM, Manojlovic NS, Marinca MV, Petrov P, Cherciu N, Ganea D, Ciuleanu TE, Pusca IA, Beg MS, Purcell WT, Croitoru AE, Ilieva RN, Natosevic S, Nita AL, Kalev DN, Harpaz Z, Farbstein M, Silverman MH, Bristol D, Itzhak I, Fishman P. Namodenoson in Advanced Hepatocellular Carcinoma and Child-Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial. Cancers (Basel). 2021 Jan 7;13(2):187. doi: 10.3390/cancers13020187.
Results Reference
background

Learn more about this trial

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

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