Phase 2, Randomized, Double-Blind, Placebo-Controlled of... | NCT02128958

Label	Type	Description	Intervention Names
CF102	Experimental	orally q12h	Drug: CF102
Placebo tablets of CF102	Placebo Comparator	orally q12h	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
CF102	Drug	orally q12h	CF102	IB-MECA

Measure	Description	Time Frame
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.	From date of first treatment (Cycle 1 Day 1) until date of death from any cause, assessed up to 12 months

Measure	Description	Time Frame
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.

Eligibility Module

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.

Name	Affiliation	Role
Michael H Silverman	Can-Fite BioPharma Ltd	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Colorado Cancer Center		Aurora	Colorado	80045	United States
Simmons Cancer Center

PubMed Identifier	Type	Citation	Retractions
33430312	Background	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.

ID	Title	Description
FG000	CF102	CF102 25 mg capsules administered orally BID
FG001	Placebo Tablets of CF102	Placebo capsules administered orally BID

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 6, 2018	Aug 4, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

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.

Posted

Count of Participants

Participants

From date of first treatment (Cycle 1 Day 1) until date of death from any cause, assessed up to 12 months

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID
OG001	Placebo Tablets of CF102	Placebo capsules administered orally BID

Units	Counts
Participants	OG00050 OG00128

Title

Denominators

Categories

12-month Survival - Yes

Title	Measurements
	OG00016 OG0014

12-month Survival - No

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The between-treatment comparison (CF102 vs Placebo) of Overall Survival will be performed using the log rank test as the primary analysis.	Log Rank		0.536														Other

Secondary

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.

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.

Posted

Median

Inter-Quartile Range

Months

From date of first treatment (Cycle 1 Day 1) until the date of first documented progression, assessed up to 36 months

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID
OG001	Placebo Tablets of CF102	Placebo capsules administered orally BID

Secondary

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.

Posted

Median

Inter-Quartile Range

months

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

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID
OG001	Placebo Tablets of CF102	Placebo capsules administered orally BID

Secondary

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID
OG001	Placebo Tablets of CF102	Placebo capsules administered orally BID

Secondary

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID
OG001	Placebo Tablets of CF102

Secondary

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.

Posted

Mean

Standard Deviation

U/L

Baseline (Cycle 1 Day 1); Cycle 11 Day 15

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID
OG001	Placebo Tablets of CF102	Placebo capsules administered orally BID

Units	Counts

Secondary

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.

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.

Posted

Mean

Standard Deviation

ratio of patient to healthy control

Baseline (Cycle 1 Day 1) and Cycle 11 Day 1

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID
OG001

Secondary

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).

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

Posted

Geometric Mean

Geometric Coefficient of Variation

L/h

Cycle 1 Days 1, 8 and 15; Cycle 2 day 1

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID

Units	Counts
Participants	OG000

Secondary

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).

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

Posted

Geometric Mean

Geometric Coefficient of Variation

Cycle 1 Days 1, 8 and 15; Cycle 2 day 1

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID

Units	Counts
Participants	OG000

Secondary

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).

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

Posted

Geometric Mean

Geometric Coefficient of Variation

Cycle 1 Days 1, 8 and 15; Cycle 2 day 1

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID

Units	Counts
Participants	OG000

Secondary

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).

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

Posted

Geometric Mean

Geometric Coefficient of Variation

Cycle 1 Days 1, 8 and 15; Cycle 2 day 1

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID

Units	Counts
Participants	OG000

Secondary

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).

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

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

Cycle 1 Days 1, 8 and 15; Cycle 2 day 1

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID

Units	Counts
Participants	OG000

Secondary

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).

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

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

Cycle 1 Days 1, 8 and 15; Cycle 2 day 1

ID	Title	Description
OG000	CF102	CF102 25 mg capsules administered orally BID

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Subileus	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Abdominal adhesions	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected50 at risk EG0010 affected28 at risk
Ascites	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected50 at risk EG0011 affected28 at risk
Peritoneal haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0012 affected28 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Coma	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Encephalopathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Hepatic Encephalopathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected50 at risk EG0011 affected28 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Death	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Disease Progression	General disorders	MedDRA 21.0	Systematic Assessment	EG00013 affected50 at risk EG0015 affected28 at risk
Chest pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Cardiac failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Myocardial infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected50 at risk EG0011 affected28 at risk
Hepatic enzyme increased/	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Bilirubin conjugated increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0005 affected50 at risk EG0012 affected28 at risk
Malignant neoplasm progression/	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0011 affected28 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0011 affected28 at risk
Bronchitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Vena cava thrombosis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0010 affected28 at risk
Subclavian vein thrombosis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Superior vena cava occlusion	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk
Renal failure	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0011 affected28 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0008 affected50 at risk EG0015 affected28 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected50 at risk EG0013 affected28 at risk
Ascites	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected50 at risk EG0012 affected28 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0012 affected28 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected50 at risk EG0012 affected28 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected50 at risk EG0010 affected28 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected50 at risk EG0016 affected28 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected50 at risk EG0014 affected28 at risk
Asthenia	General disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected50 at risk EG0016 affected28 at risk
Chest pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected50 at risk EG0013 affected28 at risk
Disease Progression	General disorders	MedDRA 21.0	Systematic Assessment	EG00014 affected50 at risk EG0015 affected28 at risk
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected50 at risk EG0013 affected28 at risk
Oedema peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected50 at risk EG0015 affected28 at risk
Pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected50 at risk EG0012 affected28 at risk
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected50 at risk EG0012 affected28 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0012 affected28 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected50 at risk EG0010 affected28 at risk
Alanine aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 affected50 at risk EG0012 affected28 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0006 affected50 at risk EG0012 affected28 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0012 affected28 at risk
Blood bilirubin increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0013 affected28 at risk
Blood thyroid stimulating hormone increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0013 affected28 at risk
Tri-iodothyronine free decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected50 at risk EG0012 affected28 at risk
Weight decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0004 affected50 at risk EG0014 affected28 at risk
Weight increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0004 affected50 at risk EG0013 affected28 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected50 at risk EG0011 affected28 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected50 at risk EG0012 affected28 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected50 at risk EG0012 affected28 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected50 at risk EG0010 affected28 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected50 at risk EG0013 affected28 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected50 at risk EG0011 affected28 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected50 at risk EG0013 affected28 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0005 affected50 at risk EG0012 affected28 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected50 at risk EG0012 affected28 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected50 at risk EG0011 affected28 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected50 at risk EG0011 affected28 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected50 at risk EG0013 affected28 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected50 at risk EG0012 affected28 at risk

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008113	Liver Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D004066	Digestive System Diseases
D008107	Liver Diseases

ID	Title	Description
BG000	CF102	CF102 25 mg capsules administered orally BID
BG001	Placebo Tablets of CF102	Placebo capsules administered orally BID
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CF102	CF102 25 mg capsules administered orally BID	34	50	37	50	46	50
EG001	Placebo Tablets of CF102	Placebo capsules administered orally BID	24	28	20	28	26	28