Clinical trial NCT04925544: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Nasopharyngeal Cancer
Epstein-Barr Virus Related Carcinoma
Keywords: Epstein-Barr Virus
Nasopharyngeal Carcinoma
Nasopharynx cancer
VK-2019
NPC
EBNA1 inhibitor
EBV
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2021-06-14
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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
Primary purpose: TREATMENT

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

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.

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

Primary outcomes:
measure: Response rate
timeFrame: 12 months
Secondary outcomes:
measure: Progression free survival
timeFrame: 24 months
measure: Overall survival
timeFrame: 24 months
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days)
measure: Time to maximum plasma concentration (Tmax),
timeFrame: Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days)
measure: Peak Plasma Concentration (Cmax)
timeFrame: Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days)
measure: Safety profile
timeFrame: 12 months
measure: Pharmacodynamic EBV DNA
timeFrame: Day 56 (ie, Day 0 Cycle 3 after,2 (each cycle is 28-day)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford Universiy
name: A. Dimitrios Colevas
role: PRINCIPAL_INVESTIGATOR
References: