Nelfinavir for the Treatment of Gammaherpesvirus-Related Tumors

Descriptive Information
Brief Title † Nelfinavir for the Treatment of Gammaherpesvirus-Related Tumors
Official Title † A Pilot Trial of Nelfinavir for the Lytic Activation and Treatment of Gammaherpesvirus-Related Tumors
Brief Summary The goals of this study is to determine if nelfinavir can target Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) in patients with certain cancers.
Detailed Description Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are gammaherpesviruses that are associated with a variety of human cancers, including a subset of lymphomas, carcinomas, and sarcomas. In tumors the virus typically exists in a latent state. In latently infected cells, the vast majority of viral genes are not expressed and there is little to no production of infectious virions. The virus replicates in tandem with cell division using cellular machinery. This highly restricted pattern of gene expression allows the virus to evade immune recognition and clearance. Currently, the treatment approach to virally-associated malignancies is no different than the treatment approach to the same tumors where there is no viral association. Yet, the presence of virus within these tumors offers an opportunity to develop virus-specific, targeted therapies in these diseases. Such therapies might not only be more effective but also less toxic. EBV- and KSHV-associated cancers are more common in patients with HIV, congenital immunodeficiencies, or other immunosuppression, such as transplant recipients. These patients in particular would benefit from more targeted treatment approaches to their malignancies, potentially sparing the toxicities of cytotoxic chemotherapy in an already immunocompromised patient population. Activation of lytic gene expression in virally-infected tumors may enhance tumor-specific cell killing through multiple mechanisms. Importantly, the cytotoxic effects of antiviral nucleoside analogues, such as acyclovir and its cogeners, depend on the activity of viral kinases which are only expressed during lytic replication. Because EBV(+) or KSHV(+) tumors are characterized by latent viral infection, these antiviral drugs as a single agent are not active in these tumors. However, if lytic gene expression could be activated in virally-associated tumors, this could render EBV(+) and KSHV(+) tumor cells susceptible to killing by antiviral nucleoside analogues. Nelfinavir (NFV), an FDA-approved protease inhibitor for the treatment of HIV, has been shown to be a potent activator of lytic gene expression of EBV(+) and KSHV(+) cancer cell lines. Furthermore, NFV is able to activate lytic gene expression of EBV and KSHV at drug levels that are achievable in humans. There is also growing evidence that NFV has antitumor activity. The goals of this study is to determine if NFV activates lytic gene expression in the tumors and causes tumor regression in patients with EBV(+) or KSHV(+) cancers.
Study Phase Phase 0
Study Type † Interventional
Study Design † Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary Outcome Measure † Lytic activation of viral gene expression by NFV
Secondary Outcome Measure † Serial assessment of methylation of viral DNA
Condition † Non-Hodgkin Lymphoma Hodgkin Lymphoma Kaposi Sarcoma Gastric Cancer Nasopharyngeal Cancer EBV Castleman Disease
Intervention † DrugNelfinavir
Study Arms / Comparison Groups Nelfinavir Nelfinavir twice daily on days 1-14 of a 14-day cycle for 4 cycles
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 10
Start Date † July 2014
Completion Date July 2016
Primary Completion Date January 2016
Eligibility Criteria † Inclusion Criteria: - Age 18 years or older - Biopsy proven EBV(+) or KSHV(+) malignancy - Relapsed/refractory disease failing > 2 prior therapies - Measurable, non-bony disease (at least one lesion on radiographic or physical exam assessment measuring > 2 cm in longest axis) - KS patients with skin-only disease must have cutaneous lesions amenable to four 3 mm punch biopsies during the course of the study - Eastern Cooperative Oncology Group (ECOG) performance status
Gender Both
Ages 18 Years - N/A
Accepts Healthy Volunteers No
Contacts †† Richard Ambinder, MD, 410-955-8839,
Location Countries † United States
Administrative Information
NCT ID † NCT02080416
Organization ID J13174
Secondary IDs †† NA_00092477
Responsible Party Sponsor
Study Sponsor † Sidney Kimmel Comprehensive Cancer Center
Collaborators ††
Investigators † Principal Investigator: Richard Ambinder, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Information Provided By
Verification Date May 2015
First Received Date † March 4, 2014
Last Updated Date May 7, 2015
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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