Clinical trial NCT02128958: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Child-Pugh Class B Cirrhosis
Lead sponsor: Can-Fite BioPharma
Sponsor class: INDUSTRY
First posted: 2014-05-01
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Number of Subjects With Overall Survival
timeFrame: From date of first treatment (Cycle 1 Day 1) until date of death from any cause, assessed up to 12 months
Secondary outcomes:
measure: Time to Progression (TTP)
timeFrame: From date of first treatment (Cycle 1 Day 1) until the date of first documented progression, assessed up to 36 months
measure: Time to Progression-Free Survival (PFS)
timeFrame: 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
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: 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
measure: Summary Statistics of Laboratory Parameters Associated With Viral Hepatitis, Hepatic Dysfunction, and Cirrhosis
timeFrame: Baseline (Cycle 1 Day 1); Cycle 11 Day 15
measure: Summary Statistics of White Blood Cell (WBC) Adenosine A3 Receptor (A3AR) Expression and Clinical Response - WBC Adenosine A3 Receptor (A3AR) Expression
timeFrame: Baseline (Cycle 1 Day 1) and Cycle 11 Day 1
measure: Pharmacokinetics (PK) Parameters of CF102 - CL/F (L/h)
timeFrame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
measure: Pharmacokinetics (PK) Parameters of CF102 - Vc/F (L)
timeFrame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
measure: Pharmacokinetics (PK) Parameters of CF102 - Vp/F (L)
timeFrame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
measure: Pharmacokinetics (PK) Parameters of CF102 - Vss/F (L)
timeFrame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
measure: Pharmacokinetics (PK) Parameters of CF102 - Elimination Half-life (Hours)
timeFrame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
measure: Pharmacokinetics (PK) Parameters of CF102 - AUC_0-12, Steady State (ng*h/mL)
timeFrame: Cycle 1 Days 1, 8 and 15; Cycle 2 day 1
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Dallas
country: United States
facility: Simmons Cancer Center
state: Texas
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center - Plovdiv
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Central Onco Hospita
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Tokuda Hospital Sofia" AD
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment for women's health - Nadezhda
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Serdica
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Sveta Marina" EAD
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni - Sectia Oncologie Medicala
city: Cluj
country: Romania
facility: Clinica Bendis - Oncologie Medicala
city: Craiova
country: Romania
facility: Centrul de Oncologie ONCOLAB
city: Iaşi
country: Romania
facility: Institutul Regional de Oncologie Iasi - Sectia Oncologie Medicala
city: Oradea
country: Romania
facility: Spitalul Pelican Impex SRL- Sectia Oncologie Medicala
city: Ploieşti
country: Romania
facility: SC DACMED SRL - Oncologie
city: Sibiu
country: Romania
facility: Spitalului Clinic Judetean de Urgenta - Sectia Oncologie Medicala
city: Suceava
country: Romania
facility: Spitalul Judetean de Urgenta "Sf. Ioan Cel Nou" - sectia Oncologie Medicala
city: Belgrade
country: Serbia
facility: Vojnomedicinska Akademija Beograd
city: Kladovo
country: Serbia
facility: Zdravstveni Centar Kladovo Služba Onkologije
city: Niš
country: Serbia
facility: Klinički Centar Niš Klinika za Onkologiju
city: Sremska Kamenica
country: Serbia
facility: Institut za Onkologiju Vojvodine
Study officials:
affiliation: Can-Fite BioPharma Ltd
name: Michael H Silverman
role: STUDY_DIRECTOR
References:
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.