An Early Phase 1 interventional study of Nelfinavir in Non-Hodgkin Lymphoma, Hodgkin Lymphoma and Kaposi Sarcoma, sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-06-10.
Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Early Phase 1, Interventional, and Treatment
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.
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.
162 studies on the registry are indexed under Sarcoma, Kaposi; 29 are open to participants now.
This study's enrollment of 1 is below the median of 32 across 114 interventional studies indexed under Sarcoma, Kaposi.
Browse Sarcoma, Kaposi studies →Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is the lead sponsor of 572 studies on the registry; 73 are open to participants now.
Of its 111 completed or terminated interventional studies of FDA-regulated products, 67 (60%) have results posted.
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Exclusion Criteria:
Nelfinavir twice daily on days 1-14 of a 14-day cycle for 4 cycles
Drug: Nelfinavir
Nelfinavir will be given 3000 mg orally twice daily on days 1-14 of a 14-day cycle. NFV will be continued in patients tolerating therapy for 4 cycles (8 weeks).
Also known as: Viracept®
Lytic activation of viral gene expression by NFV
To determine if NFV activates lytic gene expression in the tumors of patients with EBV(+) or KSHV(+) cancers, as evidenced by the ability to image the tumor with \[124I\]fialuridine-PET-CT.
Time frame: Day 4 and day 5 of Cycle 1
Serial assessment of methylation of viral DNA
The methylation of viral DNA in plasma at baseline and during the course of NFV therapy and follow-up will be determined for each patient.
Time frame: Day 4 of Cycle 1, at the end of cycles 1-4, 2 weeks post-treatment, and 4 weeks post-treatment
Serial assessment of viral copy number in plasma
Viral DNA copy number in plasma at baseline and during the course of NFV therapy and follow-up will be determined for each patient by quantitative polymerase chain reaction assay (qPCR).
Time frame: Day 4 of Cycle 1, at the end of cycles 1-4, 2 weeks post-treatment, and 4 weeks post-treatment
Tolerability of high-dose nelfinavir
The tolerability of high-dose NFV in patients with relapsed/refractory EBV(+) or KSHV(+) tumors will be determined by evaluation of dose limiting toxicities (DLT).
Time frame: Every week up to 2 weeks post-treatment
Tumor regression and response
The responses of EBV(+) and KSHV(+) tumors after 4 cycles of NFV therapy will be assessed by CT for solid tumors, CT or PET-CT for lymphomas and lymphoproliferative disorders, and skin exam with lesion measurements for KS.
Time frame: Within 2 weeks of ending treatment
Plan to share: No — Study terminated; no data analysis completed
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This study is terminated, as verified in Jun 2016. You cannot join it, but the record below documents what was studied.
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins