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

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ClinicalTrials.gov Identifier: NCT04925544
Recruitment Status : Recruiting
First Posted : June 14, 2021
Last Update Posted : April 8, 2022
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
A. Dimitrios Colevas, Stanford University

Brief Summary:
To evaluate the anti cancer effect of VK 2019 in subjects with EBV related nasopharyngeal carcinoma (NPC) for whom there is no other standard treatment available

Condition or disease Intervention/treatment Phase
Nasopharyngeal Cancer Epstein-Barr Virus Related Carcinoma Drug: VK-2019 Phase 2

Detailed Description:

Primary Objective: To characterize the anti tumor effect of VK 2019 in subjects with EBV related cancer.

Secondary Objective: 1. To characterize the safety profile, survival, PK and PD in the studied subject populations 2. To explore clinical activity and safety on subjects with post transplant lymphoproliferative disorder (PTLD) and EBV related lymphoma.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Two stage phase 2 single arm trial with three strata:

  1. EBV related NPC subjects receiving VK 2019
  2. EBV related lymphoma subjects receiving VK 2019
  3. EBV related PTLD subjects receiving VK 2019
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 25, 2022
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Viral Infections

Arm Intervention/treatment
Experimental: VK-2019_arm
1800 mg VK 2019 once daily, cycles will be defined as 28 days of treatment, subjects will receive VK 2019 until progression or dose limiting toxicity, for up to 12 cycles.
Drug: VK-2019
VK-2019 binds to EBNA1 and inhibits EBNA1 DNA binding activity. VK-2019 API is synthesized by Anthem BioSciences Pvt. Ltd and formulated into capsules by Emerson Resources Inc,




Primary Outcome Measures :
  1. Response rate [ Time Frame: 12 months ]
    Response rate to VK 2019 in EBV related NPC subjects will be assessed using RECIST v 1.1 criteria. Response Evaluable Subjects: All treated subjects with measurable disease at baseline and one of the following: 1) at least one post dose tumor assessment, 2) discontinuation prior to the first efficacy assessment due to clinical disease progression or toxicity or 3) death either on treatment or within 28 days of last VK 2019 dose.


Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 24 months ]
    Progression free survival (PFS) per RECIST v 1.1 from time of subject registration. Reported as the number of subjects remaining alive at the assessment timepoint, without progression.

  2. Overall survival [ Time Frame: 24 months ]
    Overall survival from time of subject registration. Reported as the number of subjects remaining alive at the assessment timepoint.

  3. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days) ]
    Area under the plasma concentration (AUC) for VK 2019 and metabolites will be estimated using non compartmental analysis. Analysis population is defined as all enrolled subjects treated who have at least one of the PK parameters of interest. The median AUC values by cohort, with standard deviation, obtained after 2 cycles will be reported.

  4. Time to maximum plasma concentration (Tmax), [ Time Frame: Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days) ]
    Time to maximum plasma concentration (Tmax) for VK 2019 and metabolites will be collected, Analysis population is defined as all enrolled subjects treated who have at least one of the PK parameters of interest. The median value of Tmax by cohort, with standard deviation, obtained after 2 cycles will be reported.

  5. Peak Plasma Concentration (Cmax) [ Time Frame: Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days) ]
    Maximum plasma concentration (Cmax) will be collected. Analysis population is defined as all enrolled subjects treated who have at least one of the PK parameters of interest. The median value of Cmax by cohort, with standard deviation, obtained after 2 cycles will be reported.

  6. Safety profile [ Time Frame: 12 months ]
    Measure the number of adverse events (AEs), Serious adverse events (SAEs), and Dose Limiting Toxicities (DLTs) by cohort, for up to 12 months.

  7. Pharmacodynamic EBV DNA [ Time Frame: Day 56 (ie, Day 0 Cycle 3 after,2 (each cycle is 28-day) ]
    Median difference from treatment to Day 56 (ie, Day 0 Cycle 3 after 2 28-day cycles) for the levels of cell free plasma EBV DNA by cohort, with standard deviation will be measured



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04925544


Contacts
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Contact: Elizabeth Winters 650-721-6509 ewinters@stanford.edu

Locations
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United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Elizabeth Winters    650-721-6509    ewinters@stanford.edu   
Principal Investigator: A. Dimitrios Colevas         
Sponsors and Collaborators
Stanford University
National Institutes of Health (NIH)
Investigators
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Principal Investigator: A. Dimitrios Colevas Stanford Universiy
  Study Documents (Full-Text)

Documents provided by A. Dimitrios Colevas, Stanford University:
Informed Consent Form  [PDF] March 31, 2022

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Responsible Party: A. Dimitrios Colevas, Professor of Medicine (Oncology) and of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy), Stanford University
ClinicalTrials.gov Identifier: NCT04925544    
Other Study ID Numbers: IRB-59886
VAR0207 ( Other Identifier: OnCore )
5R01CA235633 ( U.S. NIH Grant/Contract )
First Posted: June 14, 2021    Key Record Dates
Last Update Posted: April 8, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by A. Dimitrios Colevas, Stanford University:
Epstein-Barr Virus
Nasopharyngeal Carcinoma
Nasopharynx cancer
VK-2019
NPC
EBNA1 inhibitor
EBV
Additional relevant MeSH terms:
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Epstein-Barr Virus Infections
Nasopharyngeal Neoplasms
Nasopharyngeal Carcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Virus Diseases
Infections
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases