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| ID | Type | Description | Link |
|---|---|---|---|
| VAR0207 | Other Identifier | OnCore | |
| 5R01CA235633 | U.S. NIH Grant/Contract | View source | |
| NCI-2022-02830 | Registry Identifier | National Cancer Institute Clinical Trials Reporting Program |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
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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
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VK-2019_arm | Experimental | Dose escalation and expansion up to 31 additional patients at a maximum of 1800 mg twice 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VK-2019 | Drug | 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, |
| Measure | Description | Time Frame |
|---|---|---|
| Response rate | 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. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival | 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. | 24 months |
| Overall survival |
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Inclusion Criteria:
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.
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| A. Dimitrios Colevas | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Stanford | California | 94305 | United States |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Jun 25, 2024 | Oct 29, 2024 |
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Two stage phase 2 single arm trial with three strata:
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Overall survival from time of subject registration. Reported as the number of subjects remaining alive at the assessment timepoint.
| 24 months |
| Area under the plasma concentration versus time curve (AUC) | 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. | Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days) |
| Time to maximum plasma concentration (Tmax), | 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. | Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days) |
| Peak Plasma Concentration (Cmax) | 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. | Day 56 (ie, Day 0 Cycle 3 after 2, (each cycle is 28 days) |
| Safety profile | Measure the number of adverse events (AEs), Serious adverse events (SAEs), and Dose Limiting Toxicities (DLTs) by cohort, for up to 12 months. | 12 months |
| Pharmacodynamic EBV DNA | 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 | Day 56 (ie, Day 0 Cycle 3 after,2 (each cycle is 28-day) |
| ICF_002.pdf |
| ID | Term |
|---|---|
| D009303 | Nasopharyngeal Neoplasms |
| D020031 | Epstein-Barr Virus Infections |
| D000077274 | Nasopharyngeal Carcinoma |
| ID | Term |
|---|---|
| D010610 | Pharyngeal Neoplasms |
| D010039 | Otorhinolaryngologic Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009302 | Nasopharyngeal Diseases |
| D010608 | Pharyngeal Diseases |
| D009057 | Stomatognathic Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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