Testing a new drug for patients with EBV-related nasopharyngeal cancer

Phase 2, Open-label, Clinical Trial of a Novel Small Molecule EBNA1 Inhibitor, VK 2019, in Patients With Epstein Barr Virus Positive Nasopharyngeal Cancer (NPC) and Other EBV-associated Cancers, With Pharmacokinetic and Pharmacodynamic Correlative Studies

This study is testing a new drug called VK 2019 to see if it can help people with EBV-related nasopharyngeal cancer and other cancers when there are no other treatment options available.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 61 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Stanford University (other)
• Drugs / interventions: radiation
• Locations: 1 site (Stanford, California)
• Trial ID: NCT04925544 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of VK 2019, a novel small molecule inhibitor, in treating patients with Epstein-Barr Virus (EBV)-positive nasopharyngeal carcinoma and other EBV-associated cancers. The primary objective is to assess the anti-tumor effects of VK 2019 in patients who have no other standard treatment options available. Additionally, the study will investigate the safety profile, pharmacokinetics, and pharmacodynamics of the drug, as well as its clinical activity in patients with post-transplant lymphoproliferative disorder (PTLD) and EBV-related lymphoma. Participants will undergo thorough monitoring to evaluate treatment responses and side effects.

Who should consider this trial

Good fit: Ideal candidates include individuals with loco-regionally recurrent or metastatic EBV-positive nasopharyngeal carcinoma who are not eligible for other standard therapies.

Not a fit: Patients with EBV-related cancers that are amenable to curative treatment or those who are eligible for other approved therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with limited choices for EBV-related cancers.

How similar studies have performed: While this approach is novel, other studies targeting EBV-related malignancies have shown promise, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* 1 Informed consent obtained prior to any protocol mandated study specific procedures in accordance with institutional policies.
* 2 Either loco regionally recurrent or metastatic EBV positive RECIST evaluable nasopharyngeal carcinoma not amenable to curative treatment with no accepted effective standard of care therapeutic option.

Addendum for phase 2 exploratory cohorts: subjects with PTLD or EBV lymphoma not amenable to curative treatment with no accepted effective standard of care therapeutic option.

* 3 Not eligible for other approved or standard therapies
* 4.Prior palliative radiation must have been completed at least 2 weeks prior to study Cycle 1 Day 0
* 5.Prior anti cancer systemic treatment must have been completed greater than 4 weeks prior to the first dose of VK 2019 or subjects must have recovered from all acute prior treatment related AEs
* 6.Toxicities related to prior anti cancer therapy must have returned to Grade 1 or less. Peripheral neuropathy must be Grade 2 or less. Chronic but stable toxicities Grade \> 1 (eg, dysphasia, G tube dependence, etc.) are permissible.
* 7.Age ≥ 18
* 8.Absolute neutrophil count \> 1500/µL (stable off any growth factor for at least 1 week of study drug administration)
* 9.Hemoglobin \> 9g/dL (transfusion to achieve this level is permitted)
* 10.Platelet count \> 75 x 103/ µL (transfusion to achieve this level is NOT permitted)
* 11.Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) .Total serum bilirubin ≤ 1.5 x ULN
* 12.Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min as calculated per Cockcroft Gault equation
* 13.Urinary protein \< 2+ by dipstick. If dipstick ≥ 2+, then a 24 hour urine collection can be done and the subject may enter only if urinary protein is \< 1 g/24 hour
* 14.Sexually active subjects must agree to utilize birth control method during treatment and for 18 weeks after the last dose of VK 2019.
* 15.Eastern Cooperative Oncology Group (ECOG) performance status 2 or less.
* 16.Ability to understand and the willingness to personally sign the written IRB approved informed consent document.

Exclusion Criteria:

* 1.Prior therapy restrictions.
* 2.Concurrent treatment with systemic cancer directed therapy including complementary, alternative, herbal or nutritional supplement based treatments whose purpose is for anti cancer effect
* 3.Severe or active symptomatic cardiopulmonary diseases, including unstable angina, congestive heart failure, or peripheral vascular disease within 12 months prior to study drug administration; and/or chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization within 4 weeks prior to study drug administration. Subjects with effectively treated conditions (eg, stenting for coronary artery disease) are eligible if stable for at least 4 weeks prior to study drug administration
* 4.Metastatic disease with active central nervous system (CNS) involvement, defined as parenchymal brain involvement. Subjects with cranial nerve or base of skull involvement without the above are eligible. Subjects with CNS metastases that are stable on imaging at least 1 month following focal treatment with radiation are eligible
* 5.Known history of human immunodeficiency virus (HIV) unless the HIV positive subjects has:

  1. A stable regimen of highly active anti retroviral therapy (HAART)
  2. No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
  3. A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR based test
* 6.Serious uncontrolled medical disorder or active infection which would, in the opinion of the Investigator, impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy
* 7.NPC subjects: Have received a prior organ allograft or allogeneic bone marrow transplant.
* 8.Current non prescription drug or alcohol dependence
* 9.For all female subjects: pregnancy or breastfeeding
* 10.All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment
* 11.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the subject inappropriate for entry into the study
* 12.Corrected QT by Fridericia's formula (QTcF) of \> 470 ms average (mean) on triplicate ECG performed during screening

Where this trial is running

Stanford, California

• Stanford University — Stanford, California, United States (RECRUITING)

Study contacts

• Principal investigator: A. Dimitrios Colevas — Stanford Universiy
• Study coordinator: Elizabeth Winters

Conditions: Nasopharyngeal Cancer, Epstein-Barr Virus Related Carcinoma, Epstein-Barr Virus, Nasopharyngeal Carcinoma, Nasopharynx cancer, VK-2019, NPC, EBNA1 inhibitor