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

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

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

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

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 If treatment was withdrawn due to intolerability manifested as a Grade 3 or 4 event by National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE v4.0), less than 3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.