A Phase 1-2 Study of CF102 in Patients With Advanced Hepatocellular Carcinoma

NCT00790218 | Completed Phase 1 Results DMC

• 1 other identifier: CF102-102HCC
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will test the safety and efficacy of CF102 in patients with advanced liver cancer. Successive groups of patients will be given higher doses of CF102 by mouth on a twice-daily basis. Treatment will be assessed for adverse effects and for effects on the tumor.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Hepatoma; HCC

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicity

  Dose-limiting toxicity was defined as a clinically significant AE or laboratory abnormality occurring in Cycle 1

  From start of treatment until Day 28 of Cycle 1

• Maximum Tolerated Dose

  The MTD was defined as the highest dose level at which \< 2 of 6 patients developed Cycle 1 DLT.

  first 28 days (Cycle 1)

• Maximum Plasma Concentration of CF102 (Cmax)

  Blood samples were collected and plasma concentrations determined using a high-pressure liquid chromatography method.

  Dose Escalation Phase on Day 1 and Day 29 pre-dose and at 1, 2, 3, 4, 6, 8 hours post-dose

Secondary Outcomes (2)

• Number of Subjects With Objective Tumor Response

  6 months

• Relationship Between Biomarkers of Peripheral Blood Mononuclear Cell (PBMC) Adenosine A3 Receptor (A3AR) Expression and Clinical Effects of CF102

  Baseline to Day 28

Study Arms (3)

CF102 1mg

EXPERIMENTAL

An open-label trial in 28-day cycles.

Drug: CF102

CF102 5mg

EXPERIMENTAL

An open-label trial in 28-day cycles.

Drug: CF102

CF102 25mg

EXPERIMENTAL

An open-label trial in 28-day cycles.

Drug: CF102

Interventions

CF102 DRUG

CF102 capsules twice daily by mouth

Also known as: 2-Chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide, Cl-IB-MECA

CF102 1mg; CF102 25mg; CF102 5mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of HCC:
• For patients without underlying cirrhosis, diagnosis of HCC documented by cytology and/or histology
• For patients with underlying cirrhosis, diagnosis of HCC established according to the American Association for the Study of Liver Diseases Practice Guideline algorithm (Appendix V).
• HCC is advanced, refractory, or metastatic, and no standard therapies are expected to be curative.
• At least 18 years of age.
• For subjects in the dose-confirmation (RP2D) phase only: Measurable disease, using Response Evaluation Criteria in Solid Tumors (RECIST, Appendix IV). (Note that a lesion that has been subjected to radiotherapy or chemoembolization cannot be used as a target lesion.)
• Eastern Collaborative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at baseline.
• The following laboratory values must be documented within 3 days prior to initiation of study drug:
• Absolute neutrophil count (ANC) greater than or equal to 1 x 109/L
• Platelet count greater than or equal to 50 x 109/L
• Serum creatinine less than or equal to 2.0 mg/dL
• Aspartic aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit of normal.
• Total bilirubin ≤ 3.0 mg/dL.
• Serum albumin ≥ 3.0 g/dL.
• International normalized ratio (INR) ≤ 2.3.

You may not qualify if:

• Any chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, corticosteroids \> 20 mg/day prednisone or equivalent, or growth factor treatment (e.g., erythropoietin) within 14 days prior to initiation of study drug.
• Major surgery or radiation therapy within 28 days prior to initiation of study drug.
• Severe liver dysfunction (Child-Pugh Class C or hepatic encephalopathy).
• Active infection requiring systemic therapy.
• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), 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.
• Women of childbearing potential, unless they agree to use dual contraceptive methods which, in the opinion of the Principal Investigator (PI), are effective and adequate for that patient's circumstances while on study drug.
• Men who partner with a woman of childbearing potential, unless they agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable, or barrier method) while on study drug.
• Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness.
• Any severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the investigator's opinion, would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Can-Fite BioPharma: lead

Study Sites (1)

Rabin Medical Center

Tel Aviv, Israel

Location

Related Publications (2)

• Bar-Yehuda S, Stemmer SM, Madi L, Castel D, Ochaion A, Cohen S, Barer F, Zabutti A, Perez-Liz G, Del Valle L, Fishman P. The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-kappaB signal transduction pathways. Int J Oncol. 2008 Aug;33(2):287-95.

  PMID: 18636149 BACKGROUND

• Stemmer SM, Benjaminov O, Medalia G, Ciuraru NB, Silverman MH, Bar-Yehuda S, Fishman S, Harpaz Z, Farbstein M, Cohen S, Patoka R, Singer B, Kerns WD, Fishman P. CF102 for the treatment of hepatocellular carcinoma: a phase I/II, open-label, dose-escalation study. Oncologist. 2013;18(1):25-6. doi: 10.1634/theoncologist.2012-0211. Epub 2013 Jan 8.

  PMID: 23299770 DERIVED

Related Links

• Can-Fite BioPharma Ltd

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Sari Fishman, Director of Clincal Trials
• Organization: Can-Fite BioPharma

sari@canfite.co.il

972528998666

Study Officials

• Michael H Silverman, MD

  Can-Fite BioPharma Ltd

  STUDY DIRECTOR

• Salomon Shtemmer, MD

  Rabin Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study Arms: CF102 (1, 5, and 25 mg BID) in 28-day cycles.

Study Record Dates

• First Submitted: November 11, 2008
• First Posted: November 13, 2008
• Study Start: February 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2013
• Last Updated: May 17, 2022
• Results First Posted: February 27, 2015

Record last verified: 2022-04

Locations

IL (1)