Namodenoson Treatment of Advanced Pancreatic Cancer

CF102-222PC: A Phase 2 Open-Label Study of the Safety and Activity of Namodenoson in the Treatment of Advanced Pancreatic Adenocarcinoma

This is an open-label trial in patients with advanced pancreatic cancer. The trial will evaluate the safety, clinical activity, and pharmacokinetics of the study drug, namodenoson, in this group of patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Cancer; Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Namodenoson 25mg

Detailed Description

All patients will receive the study drug twice daily. The study drug is given as a capsule, orally (by mouth). Patients will be monitored regularly for safety. Tumor imaging will be performed approximately every two months. Patients can decide to stop the treatment with study drug at any time.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zivit Harpaz; Phone Number: +972 3 924 1114; Email: Zivit@canfite.co.il

Study Locations

• Israel
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center Institute of Oncology
    • Contact: Salomon M Stemmer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and females at least 18 years of age.
2. Histologically or cytologically confirmed pancreatic adenocarcinoma, or clinically diagnosed based upon scan results and a serum Cancer Antigen 19-9 value >1000 U/mL on at least 1 occasion.
3. Pancreatic adenocarcinoma is advanced (i.e., treatment-refractory or metastatic) and no standard therapies are expected to be curative.
4. Pancreatic adenocarcinoma has progressed on at least 1 prior systemic treatment regimen, or the patient refuses standard treatment.
5. Prior pancreatic adenocarcinoma treatment was discontinued for at least 14 days prior to the Baseline Visit.
6. Measurable or evaluable disease by RECIST v1.1.
7. Patients with a history of treated central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: disease outside the CNS is present; there is no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study; and there is no history of intracranial hemorrhage or spinal cord hemorrhage.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 2.

9. The following laboratory values must be documented prior to the first dose of study drug:

   • Absolute neutrophil count (ANC) ≥1.5 × 109/L
   • Platelet count ≥50 × 109/L
   • Creatinine clearance ≥50 mL/min (estimated glomerular filtration rate by the Cockcroft-Gault) or serum creatinine ≤2.0 mg/dL
   • Aspartate aminotransferase (AST) and Alanine transaminase (ALT) ≤10X the upper limit of normal
   • Total bilirubin ≤10 mg/dL
   • Serum albumin ≥2.0 g/dL.
10. Life expectancy of ≥8 weeks.
11. For women of childbearing potential, negative serum pregnancy test result.
12. Provide written informed consent to participate.
13. Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other trial-related procedures

Exclusion Criteria:

1. Receipt of systemic cancer therapy within 14 days prior to the Baseline Visit or concurrently during the trial.
2. Persistent toxicity ≥Grade 2 from previous cancer therapy, with the exceptions of alopecia and Grade 3 peripheral neuropathy.
3. Major surgery or radiation therapy within 14 days prior to the Baseline Visit.
4. Use of any investigational agent within the shorter of 4 weeks or 5 half-lives prior to the Baseline Visit.
5. Concomitant use of P-glycoprotein (P-gp)/breast cancer resistance protein (BCRP) inhibitors and/or substrates with a narrow therapeutic index unless the medication can be taken at least 3 hours before or after taking the investigational product.
6. Unable to swallow orally administered medication or presence of a gastrointestinal disorder likely to interfere with absorption of the study medication.
7. Uncontrolled or clinically unstable thyroid disease, per judgment of the Principal Investigator.
8. Active bacterial, viral, or fungal infection requiring systemic therapy or operative or radiological intervention.
9. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness or other immunodeficiency.
10. Active second primary malignancy (other than pancreatic adenocarcinoma) requiring treatment.
11. Uncontrolled arterial hypertension or congestive heart failure (New York Heart Association Classification 3 or 4).
12. Angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 1 month prior to initiation of study drug.
13. History of, or ongoing, cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the corrected QT interval (QTc) (Fridericia) interval to >470 msec [mean of triplicate electrocardiogram measurements] (patients with bundle branch block or a cardiac pacemaker will not be excluded for QTc reasons).
14. Pregnant or lactating female.
15. Women of childbearing potential, unless they agree to use dual contraceptive methods which, in the opinion of the Investigator, are effective and adequate for the patient's circumstances while on study drug and for at least 1 month thereafter.
16. 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 and for 1 month afterward.
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 patient inappropriate for entry into this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Namodenoson 25 mg; namodenoson capsule, 25 mg, administered orally, twice daily for consecutive 28-day cycles	Drug: Namodenoson 25mg; oral capsule; Other Names: CF102

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Change from baseline	Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), which is a scale of functioning, from 0 (normal activity) to 5 (death)	Every 2 weeks, assessed up to 1 year
Adverse Events	Assessments of adverse events (AEs) will include characterization of type, incidence, severity (graded by CTCAE v5.0), seriousness, and relationship to treatment.	Every 2 weeks, assessed up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	clinical activity measure of objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), measured by computed tomography (CT) scan, positron emission tomography (PET) CT, and/or magnetic resonance imaging (MRI)	Every 8 weeks, assessed up to 1 year
Progression free survival	clinical activity measure of progression free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), measured by computed tomography (CT) scan, positron emission tomography (PET) CT, and/or magnetic resonance imaging (MRI)	Every 8 weeks, assessed up to 1 year
Disease control rate	clinical activity measure of disease control rate (DCR)	Every 8 weeks, assessed up to 1 year
Duration of response	clinical activity measure of duration of response (DoR), defined as the time from first response to disease progression or death from any cause, whichever occurs first	Every 8 weeks, assessed up to 1 year
Overall survival	clinical activity measure of overall survival (OS), including death from any cause	Every 8 weeks, assessed up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life evaluation with EORTC QLQ-C30	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), in which summary scores range from 0 to 100, with higher scores indicating better health-related quality of life	Every 4 weeks, assessed up to 1 year
Quality of Life evaluation with EORTC QLQ-PAN26	European Organization for Research and Treatment of Cancer Quality of Life pancreatic adenocarcinoma-specific module, the EORTC QLQ-PAN26, in which summary scores range from 0 to 100, with higher scores indicating better health-related quality of life	Every 4 weeks, assessed up to 1 year
Pharmacokinetics of namodenoson: Cmax	Maximum plasma concentration of namodenoson	Cycle 1, day 1 (each cycle is 28 days); Cycle 1, day 15, and Cycle 2, day 1
Pharmacokinetics of namodenoson: Cmin	Minimum plasma concentration of namodenoson	Cycle 1, day 1 (each cycle is 28 days); Cycle 1, day 15, and Cycle 2, day 1
Pharmacokinetics of namodenoson: AUC(0-12)	Area under the curve of namodenoson plasma exposure from 0-12 hours post-dose	Cycle 1, day 1 (each cycle is 28 days); Cycle 1, day 15, and Cycle 2, day 1
Cancer antigen 19-9 (CA 19-9)	Change from baseline in Cancer antigen 19-9 (CA 19-9) biomarker during treatment	Every 4 weeks, assessed up to 1 year
Carcinoembryonic Antigen (CEA)	Change from baseline in Carcinoembryonic Antigen (CEA) biomarker during treatment	Every 4 weeks, assessed up to 1 year

Collaborators and Investigators

• Sponsor: Can-Fite BioPharma
• Investigators: Study Director: Michael H Silverman, MD, Can-Fite BioPharma; Principal Investigator: Salomon M Stemmer, MD, Rabin Medical Center

Publications and helpful links

General Publications

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
• Modi S, Kir D, Banerjee S, Saluja A. Control of Apoptosis in Treatment and Biology of Pancreatic Cancer. J Cell Biochem. 2016 Feb;117(2):279-88. doi: 10.1002/jcb.25284.
• Mazziotta C, Rotondo JC, Lanzillotti C, Campione G, Martini F, Tognon M. Cancer biology and molecular genetics of A3 adenosine receptor. Oncogene. 2022 Jan;41(3):301-308. doi: 10.1038/s41388-021-02090-z. Epub 2021 Nov 8.
• Itzhak I, Bareket-Samish A, Fishman P. Namodenoson Inhibits the Growth of Pancreatic Carcinoma via Deregulation of the Wnt/beta-catenin, NF-kappaB, and RAS Signaling Pathways. Biomolecules. 2023 Oct 27;13(11):1584. doi: 10.3390/biom13111584.
• Li L, Mo FK, Chan SL, Hui EP, Tang NS, Koh J, Leung LK, Poon AN, Hui J, Chu CM, Lee KF, Ma BB, Lai PB, Chan AT, Yu SC, Yeo W. Prognostic values of EORTC QLQ-C30 and QLQ-HCC18 index-scores in patients with hepatocellular carcinoma - clinical application of health-related quality-of-life data. BMC Cancer. 2017 Jan 4;17(1):8. doi: 10.1186/s12885-016-2995-5.

Helpful Links

• American Heart Association Classes of Heart Failure. www.heart.org.

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2024
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): December 15, 2026

Study Registration Dates

• First Submitted: April 15, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 2, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms
• Other Study ID Numbers: CF102-222PC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No