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Phase 1/2a Study of VK-2019 in Patients With Epstein-Barr Virus (EBV)-Positive Nasopharyngeal Carcinoma (NPC)
Trial ID: NCT03682055
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.
Phase 1/2a Open Label, Multicenter 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
1. Informed consent obtained prior to any protocol mandated assessment.
2. Age ≥ 18.
3. Either loco regionally recurrent or metastatic EBV positive nasopharyngeal carcinoma
not amenable to curative treatment. EBV positivity is defined as high EBV viral load
in plasma (> 4000 genomes per µg plasma DNA) and/or biopsy tissue positive for EBV.
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 study Cycle 1 Day 0.
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
(e.g., dysphasia, G tube dependence, etc.) may be allowed after agreement between the
Investigator and Sponsor.
7. For the dose expansion phase only: Patients must have RECIST v1.1 measurable disease,
defined as at least one lesion that can be accurately measured in at least one
dimension (longest diameter to be recorded for non nodal lesions and short axis for
nodal lesions) as ≥ 10 mM with spiral CT scan, MRI, or calipers by clinical exam.
8. ECOG performance status score of ≤ 2 at study entry.
9. Absolute neutrophil count > 1500/µL (stable off any growth factor within 1 week of
study drug administration).
10. Hemoglobin > 9g/dL (transfusion to achieve this level is permitted).
11. Platelet count > 75 x 103/ µL (transfusion to achieve this level is NOT permitted).
12. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper
limit of normal (ULN).
13. Total serum bilirubin ≤ 1.5 x ULN.
14. Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min as calculated per
Cockcroft Gault equation.
15. 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.
16. Sexually active patients must agree to utilize birth control method during the study
and for 18 weeks after the study is concluded, using effective birth control methods
as defined in
17. Willingness and ability to comply with the study scheduled visits, treatment plans,
laboratory tests and other procedures.
1. 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 (eg, stenting for CAD) are eligible.
2. 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 1
month following focal treatment with radiation are eligible.
3. Concurrent treatment with systemic cancer directed therapy including complementary,
alternative, herbal or nutritional supplement based treatments whose purpose is for
anti cancer effect.
4. Positive for human immunodeficiency virus (HIV) are not excluded from this study, but
HIV positive patients must have:
- A stable regimen of highly active anti retroviral therapy (HAART)
- No requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infections
- A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard
PCR based test
5. 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.
6. Currently taking drugs that inhibit or induce OATP1B1 or OATP1B3 within 5 half lives
of that agent. Examples are included in Appendix 2.
7. Have received a prior organ allograft or allogeneic bone marrow transplant.
8. Current non prescription drug or alcohol dependence.
9. For all female patients, pregnancy or breastfeeding.
10. All female patients 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 patient inappropriate for entry into
12. Corrected QT by Fridericia's formula (QTcF) of > 470 ms.
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