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Non-Hodgkin LymphomaEarly Phase 1NCT02080416

Nelfinavir for the Treatment of Gammaherpesvirus-Related Tumors

A Early Phase 1 study testing Nelfinavir in people with Non-Hodgkin Lymphoma and Hodgkin Lymphoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nelfinavir
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
Jul 2014to Feb 2016
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 < 2
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  • Life expectancy of greater than 12 weeks
  • Patients must be able to lie flat for at least 60 minutes and fit on a PET-CT scanner
  • Ability to comply with an oral drug regimen
  • Females of childbearing potential must have a negative pregnancy test at screening
  • Patients must have normal organ and marrow function as defined below within 14 days of study entry

Who cannot join

  • Patients with HIV-associated primary central nervous system lymphoma
  • Radiotherapy or chemotherapy ending within 14 days of study enrollment
  • Patients currently on other protease inhibitors
  • Chronic diarrhea
  • Acute, active infection within 14 days of enrollment
  • Patients on active treatment for hypo- or hyperthyroidism
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  • End-stage liver disease unrelated to tumor
  • Hepatitis B or hepatitis C infection
  • Use of any other type of investigational agent or treatment concurrently or within 28 days before the first dose of study treatment
  • History of iodine hypersensitivity
  • Females who are pregnant or breastfeeding
  • Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity, non-compliance, or inability to complete the study requirements
  • Use of drugs to treat or prevent herpesvirus infections
  • Essential medication that is known to interact with nelfinavir

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: A Pilot Trial of Nelfinavir for the Lytic Activation and Treatment of Gammaherpesvirus-Related Tumors

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.

Read the 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.

Being tested
Nelfinavir
Keywords
EBV, KSHV, malignancy, lymphoma, sarcoma, virus-associated
Medical subject headings
Lymphoma, Non-Hodgkin, Hodgkin Disease, Sarcoma, Kaposi, Stomach Neoplasms, Nasopharyngeal Neoplasms, Castleman Disease, Neoplasms, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NelfinavirDrug

    Also called Viracept®

    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).

Study groups in NCT02080416
Study groupRoleWhat they receive
NelfinavirExperimentalNelfinavir twice daily on days 1-14 of a 14-day cycle for 4 cycles
Receives: Drug: Nelfinavir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 4 and day 5 of Cycle 1

Secondary outcomes (4)

  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.

    Measured: Day 4 of Cycle 1, at the end of cycles 1-4, 2 weeks post-treatment, and 4 weeks post-treatment

  2. 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).

    Measured: Day 4 of Cycle 1, at the end of cycles 1-4, 2 weeks post-treatment, and 4 weeks post-treatment

  3. 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).

    Measured: Every week up to 2 weeks post-treatment

  4. 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.

    Measured: Within 2 weeks of ending treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2014 (estimated)
  2. Study startJul 2014
  3. Primary completionFeb 2016
  4. Study completionFeb 2016

Why it stopped: Very slow accrual; terminated to allow resources to be utilized more effectively on other studies. No data analysis completed, nor any conclusions reached.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02080416
Sponsor's protocol ID
J13174
Other IDs
NA_00092477
Status last verified
Jun 2016
First submitted
4 Mar 2014
Last updated
10 Jun 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No: Study terminated; no data analysis completed

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Nelfinavir in people with Non-Hodgkin Lymphoma and Hodgkin Lymphoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Very slow accrual; terminated to allow resources to be utilized more effectively on other studies. No data analysis completed, nor any conclusions reached.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Lytic activation of viral gene expression by NFV (time frame: Day 4 and day 5 of Cycle 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02080416.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2016.

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