Description:
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
Title
- Brief Title: 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 and Other EBV Associated Cancers, With Pharmacokinetic and Pharmacodynamic Correlative Studies
Clinical Trial IDs
- ORG STUDY ID:
IRB-59886
- SECONDARY ID:
VAR0207
- NCT ID:
NCT04925544
Conditions
- Nasopharyngeal Cancer
- Epstein-Barr Virus Related Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
VK-2019 | | VK-2019_arm |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
VK-2019_arm | Experimental | 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. | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Response rate |
Time Frame: | 12 months |
Safety Issue: | |
Description: | 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
Measure: | Progression free survival |
Time Frame: | 24 months |
Safety Issue: | |
Description: | 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. |
Measure: | Overall survival |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Overall survival from time of subject registration. Reported as the number of subjects remaining alive at the assessment timepoint. |
Measure: | 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) |
Safety Issue: | |
Description: | 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. |
Measure: | Time to maximum plasma concentration (Tmax), |
Time Frame: | Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days) |
Safety Issue: | |
Description: | 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. |
Measure: | Peak Plasma Concentration (Cmax) |
Time Frame: | Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days) |
Safety Issue: | |
Description: | 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. |
Measure: | Safety profile |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Measure the number of adverse events (AEs), Serious adverse events (SAEs), and Dose Limiting Toxicities (DLTs) by cohort, for up to 12 months. |
Measure: | Pharmacodynamic EBV DNA |
Time Frame: | Day 56 (ie, Day 0 Cycle 3 after,2 (each cycle is 28-day) |
Safety Issue: | |
Description: | 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 |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Stanford University |
Trial Keywords
- Epstein-Barr Virus
- Nasopharyngeal Carcinoma
- Nasopharynx cancer
- VK-2019
- NPC
- EBNA1 inhibitor
- EBV
Last Updated
June 14, 2021