Clinical Trials /

Phase 1-2a Study of VK-2019 in Patients With Epstein-Barr Virus (EBV)-Positive Nasopharyngeal Carcinoma (NPC)

NCT03682055

Description:

VK-2019-001 is a 1-2a trial of the oral EBNA-1 targeting agent VK-2019 in patients with EBV-positive recurrent or metastatic NPC to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D), as well as to evaluate the PK profile of VK-2019.

Related Conditions:
  • Nasopharyngeal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1-2a Study of EBNA1 Inhibitor, VK-2019, in Patients With Epstein-Barr Virus-positive Nasopharyngeal Cancer
  • Official Title: Phase 1‑2a Clinical Trial of a Novel Small Molecule EBNA1 Inhibitor, VK‑2019, in Patients With Epstein‑Barr Virus Positive Nasopharyngeal Cancer, With Pharmacokinetic and Pharmacodynamic Correlative Studies

Clinical Trial IDs

  • ORG STUDY ID: VK2019-001
  • NCT ID: NCT03682055

Conditions

  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Cancer

Interventions

DrugSynonymsArms
VK-2019Drug VK-2019 once daily oral dose

Purpose

This study is a First-In-Human clinical trial to assess the safety and preliminary efficacy of VK-2019, an orally administered EBNA1 inhibitor, for the treatment of patients with advanced nasopharyngeal carcinoma.

Detailed Description

      This is a first-in-human phase 1‑2a dose escalation‑trial of the oral EBNA1 targeting agent
      VK‑2019 in patients with Epstein-Barr Virus (EBV)-positive recurrent or metastatic
      nasopharyngeal carcinoma (NPC). Primary objectives include safety profile and PK evaluation
      to define Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D). Secondary
      objectives include evaluation of anti‑tumor effect, anti‑EBV activity, food pharmacokinetic
      (PK) effect and pharmacodynamics.

      Once daily dosing using an accelerated titration plan with intrapatient dose escalation is
      anticipated until Adverse Event (AE) rules are met for stopping the accelerated escalation
      phase, followed by reversion to a conventional 3+3 escalation plan until MTD has been
      defined.

      There will be extensive blood and urine pharmacokinetic studies performed on all patients.

      Extensive safety monitoring will include evaluation of blood counts, blood chemistries,
      urinalyses, pregnancy testing, EKGs, drug compliance and clinical evaluations focused on
      adverse event detection and monitoring.

      Efficacy evaluation will be per RECIST criteria and pharmacodynamic (PD) evaluation will
      include blood and tumor tissue evaluations. The tumor tissue biopsies for PD will be limited
      to a subset of patients at the MTD.

      There will be an expansion phase at the MTD, with a food effect sub‑study on a subset of
      patients treated at MTD.

      All treatments will be conducted at the Stanford Cancer Institute (SCI) in Stanford,
      California. There are limited funds available to support travel to the investigational site.
      We expect travel to Stanford will be feasible for many patients. An overnight stay in the SCI
      area may be necessary to collect some PK effect samples.
    

Trial Arms

NameTypeDescriptionInterventions
Drug VK-2019 once daily oral doseExperimentalEBNA1 inhibitor
  • VK-2019

Eligibility Criteria

        Inclusion Criteria:

          -  Informed consent obtained prior to any protocol mandated assessment.

          -  Age ≥ 18;

          -  Either loco-regionally recurrent or metastatic EBV-positive nasopharyngeal carcinoma
             not amenable to curative treatment.

          -  Prior palliative radiation must have been completed at least 2 weeks prior to study.

          -  Prior anti-cancer systemic treatment must have been completed greater than 4 weeks
             prior to study.

          -  Toxicities related to prior therapy must have returned to Grade 1 or less, or if
             chronic must be stable. Peripheral neuropathy must be Grade 2 or less.

          -  For the dose expansion phase only: Patients must have RECIST v1.1 measurable disease.

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2 at study
             entry;

          -  Adequate organ function as defined by the following criteria:

               1. Absolute neutrophil count > 1500/µL;

               2. Hemoglobin > 9g/dL;

               3. Platelet count > 75 X 1000/ µL;

               4. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x
                  upper limit of normal (ULN);

               5. Total serum bilirubin ≤ 1.5 x ULN;

               6. Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min as calculated
                  per Cockcroft-Gault equation;

               7. Urinary protein < 2+ by dipstick. If dipstick ≥ 2+, then a 24-hour urine
                  collection can be done and the patient may enter only if urinary protein is < 1
                  g/24 hour.

          -  Sexually active patients will agree to utilize birth control method during the study
             and for 18 weeks after the study is concluded, using effective birth control methods.

          -  Willingness and ability to comply with the study scheduled visits, treatment plans,
             laboratory tests and other procedures.

        Exclusion Criteria:

          -  Severe or active symptomatic cardiopulmonary diseases (unstable angina and/or
             congestive heart failure or peripheral vascular disease within the last 12 months;
             chronic obstructive pulmonary disease exacerbation other respiratory illness requiring
             hospitalization) or clinically significant psychiatric disorders; patients with
             effectively treated conditions (e.g. stenting for CAD) are eligible.

          -  Metastatic disease with active central nervous system (CNS) involvement, defined as
             parenchymal brain involvement. Patients with cranial nerve or base of skull
             involvement without the above are eligible; Patients with CNS metastases stable x 1
             month following focal treatment with radiation are eligible.

          -  Concurrent treatment with systemic cancer directed therapy including complementary,
             alternative, herbal or nutritional supplement-based treatments whose purpose is for
             anti-cancer effect.;

          -  Patients positive for human immunodeficiency virus (HIV) are not excluded from this
             study, but HIV-positive patients must have:

               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 Cluster of Differentiation 4 (CD4) count above 250 cells/microliter (mcL) and
                  an undetectable HIV viral load on standard Polymerase Chain Reaction (PCR)-based
                  test.

          -  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.

          -  Currently taking drugs that inhibit or induce Organic Anion Transporting Polypeptide
             family member 1B1 (OATP1B1) or Organic Anion Transporting Polypeptide family member
             1B3 (OATP1B3) within 5 half-lives of that agent.

          -  Have received a prior organ allograft or allogeneic bone marrow transplant.

          -  Current non-prescription drug or alcohol dependence;

          -  For all female patients, pregnancy or breastfeeding;

          -  All female patients with reproductive potential must have a negative pregnancy test
             (serum or urine) prior to enrollment.

          -  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 patient inappropriate for entry into
             the study.

          -  Corrected QT by Fridericia's formula (QTcF) of >470 ms.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety (Measure of number and severity of adverse events)
Time Frame:4 weeks up to more than 24 weeks (6 cycles x 4 weeks/cycle)
Safety Issue:
Description:To evaluate and characterize the safety profile of single agent VK‑2019 in adult patients with recurrent or metastatic NPC.

Secondary Outcome Measures

Measure:Pharmacokinetics (Amount of drug in plasma as assessed by the Area Under the Curve)
Time Frame:4 weeks up to more than 24 weeks (6 cycles x 4 weeks/cycle)
Safety Issue:
Description:To characterize the single‑dose and steady state pharmacokinetic Area Under the Curve (AUC) of single agent VK‑2019 in adult patients with recurrent or metastatic NPC.
Measure:Effect on tumor size
Time Frame:4 weeks up to more than 24 weeks (6 cycles x 4 weeks/cycle)
Safety Issue:
Description:To evaluate the anti‑tumor activity of single agent VK‑2019 per RECIST v1.1 in adult patients with recurrent or metastatic NPC.
Measure:Effect on Epstein-Barr Virus (plasma viral load)
Time Frame:4 weeks up to more than 24 weeks (6 cycles x 4 weeks/cycle)
Safety Issue:
Description:To evaluate the anti‑EBV activity by reduction of plasma EBV‑DNA (EBV copy number/ml of blood) of single agent VK‑2019 in adult patients with recurrent or metastatic NPC.
Measure:Food effect pharmacokinetic sub study for select patients (Amount of drug in plasma as assessed by the Area Under the Curve)
Time Frame:1 week
Safety Issue:
Description:To provide preliminary evidence of the effect of food on single dose pharmacokinetic of VK‑2019.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Troy Messick

Trial Keywords

  • Epstein-Barr Virus
  • Nasopharyngeal Carcinoma
  • NPC
  • EBV
  • EBNA1 inhibitor
  • VK-2019
  • Nasopharynx cancer
  • Nasopharynx carcinoma

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