Namodenoson Treatment of Advanced Pancreatic Cancer

Official title

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

Overview

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.

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.

Interventions

• Drug Namodenoson 25mg
  oral capsule

Primary outcome measures

• Adverse Events [Time frame: Every 2 weeks, assessed up to 1 year]
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Change from baseline [Time frame: Every 2 weeks, assessed up to 1 year]

Secondary outcome measures (5)

• Objective response rate [Time frame: Every 8 weeks, assessed up to 1 year]
• Progression free survival [Time frame: Every 8 weeks, assessed up to 1 year]
• Disease control rate [Time frame: Every 8 weeks, assessed up to 1 year]
• Duration of response [Time frame: Every 8 weeks, assessed up to 1 year]
• Overall survival [Time frame: Every 8 weeks, assessed up to 1 year]

Eligibility criteria

Inclusion criteria

• Males and females at least 18 years of age.
• 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.
• Pancreatic adenocarcinoma is advanced (i.e., treatment-refractory or metastatic) and no standard therapies are expected to be curative.
• Pancreatic adenocarcinoma has progressed on at least 1 prior systemic treatment regimen, or the patient refuses standard treatment.
• Prior pancreatic adenocarcinoma treatment was discontinued for at least 14 days prior to the Baseline Visit.
• Measurable or evaluable disease by RECIST v1.1.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 2.
• 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.
• Life expectancy of ≥8 weeks.
• For women of childbearing potential, negative serum pregnancy test result.
• Provide written informed consent to participate.
• Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other trial-related procedures

Exclusion criteria

• Receipt of systemic cancer therapy within 14 days prior to the Baseline Visit or concurrently during the trial.
• Persistent toxicity ≥Grade 2 from previous cancer therapy, with the exceptions of alopecia and Grade 3 peripheral neuropathy.
• Major surgery or radiation therapy within 14 days prior to the Baseline Visit.
• Use of any investigational agent within the shorter of 4 weeks or 5 half-lives prior to the Baseline Visit.
• 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.
• Unable to swallow orally administered medication or presence of a gastrointestinal disorder likely to interfere with absorption of the study medication.
• Uncontrolled or clinically unstable thyroid disease, per judgment of the Principal Investigator.
• Active bacterial, viral, or fungal infection requiring systemic therapy or operative or radiological intervention.
• Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness or other immunodeficiency.
• Active second primary malignancy (other than pancreatic adenocarcinoma) requiring treatment.
• Uncontrolled arterial hypertension or 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 1 month prior to initiation of study drug.
• 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).
• Pregnant or lactating female.
• 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.
• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Israel · 1 center

• Rabin Medical Center Institute of Oncology — Petah Tikva

Publications

• 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. PMID 26206252
• 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. PMID 34750517
• 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. PMID 19097774
• 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. PMID 38002266
• 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. PMID 28052758
• 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. PMID 7165009

Identifiers

NCT: NCT06387342 · CF102-222PC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗