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

• Register: ClinicalTrials.gov
• Last refreshed on: 10 October 2022
• Main ID: NCT02128958
• Date of registration: 27/04/2014
• Prospective Registration: Yes
• Primary sponsor: Can-Fite BioPharma
• Public title: Phase 2, Randomized, Double-Blind, Placebo-Controlled of the Efficacy and Safety of CF102 in Hepatocellular Carcinoma (HCC)
• Scientific title: A Phase 2 Study in the Second-Line Treatment of Advanced Hepatocellular Carcinoma in Subjects With Child-Pugh Class B Cirrhosis
• Date of first enrolment: September 2014
• Target sample size: 78
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02128958
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

Bulgaria, Israel, Romania, Serbia, United States

Contacts

• Name: Michael H Silverman
• Affiliation: Can-Fite BioPharma Ltd

Key inclusion & exclusion criteria

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treatment was withdrawn due to intolerability manifested as a Grade 3 or 4 event by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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Hepatocellular Carcinoma

Intervention(s)

Drug: CF102

Drug: Placebo

Primary Outcome(s)

Number of Subjects With Overall Survival [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(s)

Pharmacokinetics (PK) Parameters of CF102 - AUC_0-12, Steady State (ng*h/mL) [Time Frame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1]

Disease Control Rate (DCR) [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]

Pharmacokinetics (PK) Parameters of CF102 - CL/F (L/h) [Time Frame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1]

Pharmacokinetics (PK) Parameters of CF102 - Elimination Half-life (Hours) [Time Frame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1]

Objective Response Rate (ORR) [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]

Time to Progression (TTP) [Time Frame: From date of first treatment (Cycle 1 Day 1) until the date of first documented progression, assessed up to 36 months]

Time to Progression-Free Survival (PFS) [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]

Pharmacokinetics (PK) Parameters of CF102 - Vc/F (L) [Time Frame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1]

Summary Statistics of White Blood Cell (WBC) Adenosine A3 Receptor (A3AR) Expression and Clinical Response - WBC Adenosine A3 Receptor (A3AR) Expression [Time Frame: Baseline (Cycle 1 Day 1) and Cycle 11 Day 1]

Pharmacokinetics (PK) Parameters of CF102 - Vp/F (L) [Time Frame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1]

Summary Statistics of Laboratory Parameters Associated With Viral Hepatitis, Hepatic Dysfunction, and Cirrhosis [Time Frame: Baseline (Cycle 1 Day 1); Cycle 11 Day 15]

Pharmacokinetics (PK) Parameters of CF102 - Vss/F (L) [Time Frame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1]

Secondary ID(s)

CF102-201HCC

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/12/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02128958