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

April 23, 2022 updated by: Can-Fite BioPharma

A Phase 1-2, Open-label, Dose-escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered CF102 in Patients With Advanced Hepatocellular Carcinoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, open-label, non-randomized, dose-escalation study, to be conducted in 2 phases: a dose-escalation phase, to determine the MTD of CF102 and to evaluate its safety/tolerability, PK, pharmacodynamic, and preliminary clinical activity; and a dose-confirmation phase, which will be a cohort expansion at or below the MTD (ie, the RP2D) of CF102. Subjects will be treated with oral doses of CF102 in consecutive, 28-day cycles. The initial dose of CF102 will be 1 mg twice daily (BID), with subsequent escalations to 5 and 25 mg BID, unless limited by toxicity. Subjects will be evaluated weekly for the first cycle, every 2 weeks for Cycles 2 and 3, and at the end of each subsequent cycle, up to 6 cycles of CF102 treatment. Subjects will return for a follow-up visit 28 days after completion of the last dose of study drug.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Tel Aviv, Israel
        • Rabin Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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).
  2. HCC is advanced, refractory, or metastatic, and no standard therapies are expected to be curative.
  3. At least 18 years of age.
  4. 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.)
  5. Eastern Collaborative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at baseline.

  6. 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.
  7. Esophageal bleeding and varices, if present, have been sclerosed or banded, and no bleeding episodes have occurred during the prior 6 months.
  8. Life expectancy of ≥ 12 weeks.
  9. For women of childbearing potential, negative serum pregnancy test result.
  10. Absence of active malignancy other than HCC within 2 years of entry, with the exception of basal cell carcinoma and squamous cell carcinoma of the skin.
  11. Provide written informed consent to participate.

  12. Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other study related procedures.

    -

Exclusion Criteria:

  1. 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.
  2. Major surgery or radiation therapy within 28 days prior to initiation of study drug.
  3. Severe liver dysfunction (Child-Pugh Class C or hepatic encephalopathy).
  4. Active infection requiring systemic therapy.
  5. 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.
  6. 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.
  7. Pregnant or lactating female.
  8. 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.
  9. 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.
  10. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness.

  11. 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.

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CF102 1mg
An open-label trial in 28-day cycles.
Drug: CF102
CF102 capsules twice daily by mouth
Other Names:
  • Cl-IB-MECA
  • 2-Chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide
Experimental: CF102 5mg
An open-label trial in 28-day cycles.
Drug: CF102
CF102 capsules twice daily by mouth
Other Names:
  • Cl-IB-MECA
  • 2-Chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide
Experimental: CF102 25mg
An open-label trial in 28-day cycles.
Drug: CF102
CF102 capsules twice daily by mouth
Other Names:
  • Cl-IB-MECA
  • 2-Chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Limiting Toxicity
Time Frame: From start of treatment until Day 28 of Cycle 1
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
Time Frame: first 28 days (Cycle 1)
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)
Time Frame: Dose Escalation Phase on Day 1 and Day 29 pre-dose and at 1, 2, 3, 4, 6, 8 hours post-dose
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects With Objective Tumor Response
Time Frame: 6 months
Therapeutic effect of CF102 in hepatocellular carcinoma measured by 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
Time Frame: Baseline to Day 28
The Peripheral Blood Mononuclear Cells (PBMC) were to be collected at Baseline and Day 28 in order to evaluate the Adenosine A3 receptor (A3AR) and PBMC biomarkers, and clinical effects of CF102.
Baseline to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Can-Fite BioPharma

Investigators

  • Study Director: Michael H Silverman, MD, Can-Fite BioPharma Ltd
  • Principal Investigator: Salomon Shtemmer, MD, Rabin Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2009

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

November 11, 2008

First Submitted That Met QC Criteria

November 11, 2008

First Posted (Estimate)

November 13, 2008

Study Record Updates

Last Update Posted (Actual)

May 17, 2022

Last Update Submitted That Met QC Criteria

April 23, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CF102-102HCC

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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