Nelfinavir Mesylate in Treating Patients With Kaposi Sarcoma

NCT03077451 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: AMC-098NCI-2016-00071AMC 0982UM1CA121947
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 12

Brief Summary

This pilot phase II trial studies how well nelfinavir mesylate works in treating patients with kaposi sarcoma. Nelfinavir mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Kaposi Sarcoma; Skin Kaposi Sarcoma

Outcome Measures

Primary Outcomes (2)

• Efficacy of Therapeutic Escalation of Standard Dose Nelfinavir, Followed by High Dose Nelfinavir, for Treatment of Kaposi Sarcoma Lesions for HIV Positive Participants

  The binomial proportion and its exact 95% confidence interval will be used to estimate the overall response rate in the study. Overall response is defined as Complete response or partial response. Response and progression will be evaluated in this study using the AIDS Clinical Trials Groups (ACTG) response criteria for Kaposi sarcoma. Complete response (CR) is defined as the absence of any detectable residual disease, including tumor-associated edema, persisting for at least 4 weeks. Partial response (PR) is defined as no new lesions (skin or oral), or new visceral sites of involvement (or the appearance or worsening of tumor-associated edema or effusions); 50% or greater decrease in the number of all previously existing lesions lasting for at least 4 weeks; OR Complete flattening of at least 50% of all previously raised lesions; OR 50% decrease in the sum of the products of the largest perpendicular diameters of the marker lesions.

  Baseline up to 16 weeks

• Efficacy of Therapeutic Escalation of Standard Dose Nelfinavir, Followed by High Dose Nelfinavir, for Treatment of Kaposi Sarcoma Lesions for HIV Negative Participants

  The binomial proportion and its exact 95% confidence interval will be used to estimate the response rate in the study. Response rate will be estimated using the binomial proportion and it's exact 95% confidence interval for HIV negative participants.

  Baseline up to 16 weeks

Secondary Outcomes (5)

• Frequency and Severity of Adverse Events in HIV-positive Participants as Assessed by CTCAE v4.0

  Baseline to up to 16 weeks

• Frequency and Severity of Adverse Events in HIV-negative Participants as Assessed by CTCAE v4.0

  Baseline to up to 16 weeks

• Assess the Effect of Nelfinavir on KSHV Gene Expression in Tumor Tissue

  Baseline to up to 16 weeks

• Correlate Nelfinavir and the Primary Active Metabolite, M8, Concentrations With Tumor Response, Antiviral Response, and Adverse Effects in Participants With KS.

  Baseline to up to 16 weeks

• Assess the Effect of Nelfinavir on KSHV Copy Number in Saliva

  Up to 16 weeks

Study Arms (1)

Treatment (nelfinavir mesylate)

EXPERIMENTAL

DOSE NELFINAVIR MESYLATE: Patients receive standard dose nelfinavir mesylate PO BID for 4 weeks in the absence of PD. Patients with PD at 4 weeks proceed to high-dose nelfinavir. At week 8, if there is SD or PR, patients advance to high-dose nelfinavir mesylate. Patients discontinue standard dose nelfinavir mesylate 4 weeks after documentation of CR. HIGH DOSE NELFINAVIR MESYLATE: Patients with PD continue to receive high-dose nelfinavir mesylate PO BID for 4 more weeks. If there is PD documented after 4 weeks at the high dose level, nelfinavir is discontinued. If there is SD or PR, patients continue receiving nelfinavir mesylate for 16 weeks. If there is CR, patients discontinue high-dose nelfinavir mesylate 4 weeks after documentation of CR.

Other: Laboratory Biomarker Analysis; Drug: Nelfinavir Mesylate

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nelfinavir mesylate)

Nelfinavir Mesylate DRUG

Given PO

Also known as: AG1343, Viracept

Treatment (nelfinavir mesylate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy-proven KS involving skin (with or without visceral involvement) without need for urgent cytotoxic therapy; there should be no evidence of improvement in KS in the 4 weeks immediately prior to study enrollment
• Known human immunodeficiency virus (HIV)-1 infection status, as documented by any nationally approved, licensed HIV rapid test performed in conjunction with screening (or enzyme-linked immunosorbent assay \[ELISA\], test kit, and confirmed by approved test at each study site; United States (U.S.) participants only: alternatively, this documentation may include a record demonstrating that another physician has documented the participant's HIV status based on either:
• Approved diagnostic tests, or
• The referring physician's written record that HIV infection was documented, with supporting information on the participant's relevant medical history and/or current management of HIV infection
• Participants enrolled outside the U.S. must have a confirmatory diagnostic test sequence as appropriate per national standards, detailed as above, performed regardless of prior documented HIV status; for HIV-negative participants, testing must be performed no more than 1 month prior to study enrollment; NOTE: the term "licensed" refers to a U.S. Food and Drug Administration (FDA)-approved kit or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally; WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment; a reactive initial rapid test should be confirmed by either another type of rapid assay or an enzyme/chemiluminescence immunoassay (E/CIA) that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 ribonucleic acid (RNA) viral load
• Participant may be either previously untreated for KS or refractory to or intolerant of any one or more prior KS therapies
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%)
• Life expectancy of greater than 3 months
• Leukocytes \>= 3,000/mm\^3
• Absolute neutrophil count \>= 1,500/mm\^3
• Platelets \>= 100,000/mm\^3
• Total bilirubin: within normal limits at each study site local laboratory
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine transaminase (ALT) (serum glutamate-pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal
• Creatinine levels =\< upper limit of institutional normal; or creatinine clearance \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal
• HIV seropositive participants must be on antiretroviral therapy (ART) with the following criteria:

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study enrollment or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to study enrollment
• Participants who are receiving any other investigational agents
• Participants with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nelfinavir
• Participants receiving any medications or substances that have antiviral activity against KSHV or that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A (CYP3A) or cytochrome P450, family 2, subfamily C, polypeptide 19 (2C19) are ineligible; each ART regimen must be reviewed by the PI before determining eligibility to receive nelfinavir mesylate (NFV); sensitive substrates should be avoided; of the antiretroviral drugs, only delavirdine, nevirapine, cobicistat-boosted antiretrovirals (strong CYP3A4 inhibitor), maraviroc (sensitive CYP3A4 substrate), and PIs (strong CYP3A4 inhibitor) are excluded; the following drugs are also prohibited:
• Strong Inhibitors of CYP3A4:
• Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin
• HIV: non-nucleoside reverse transcriptase inhibitors (delavirdine, nevirapine), protease inhibitors (ritonavir, indinavir, lopinavir/ritonavir, saquinavir), cobicistat-boosted antiretrovirals (e.g., elvitegravir); NOTE: Clinical trials have demonstrated that there are no clinically significant drug-drug interactions between nelfinavir and the following antiretrovirals: efavirenz (strong CYP3A4 inhibitor), etravirine (strong CYP3A4 inhibitor); therefore, these antiretrovirals will not be excluded
• Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole, posaconazole
• Antidepressants: nefazodone
• Antidiuretic: conivaptan
• GI: cimetidine, aprepitant
• Hepatitis C: boceprevir, telaprevir
• Miscellaneous: seville oranges, grapefruit, or grapefruit juice and/or pomelos, star fruit, exotic citrus fruits, or grapefruit hybrids
• Strong Inducers of CYP3A4:

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• The Emmes Company, LLC: collaborator
• University of Arkansas: collaborator
• University of California, Los Angeles: collaborator
• AIDS and Cancer Specimen Resource: collaborator
• Montefiore Medical Center: collaborator
• AIDS Malignancy Consortium: lead

Study Sites (12)

University of Miami

Miami, Florida, 33136, United States

Location

Emory University/Grady Hospital

Atlanta, Georgia, 30308, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Benaroya Research Institute at Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

African Cancer Institute, Stellenbosch University

Cape Town, South Africa

Location

Uganda Cancer Institute

Kampala, Uganda

Location

MeSH Terms

Conditions

Sarcoma, Kaposi

Interventions

Nelfinavir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Deukwoo Kwon
• Organization: Statistical and Data Analysis Center, AIDS Malignancy Consortium

deukwoo.kwon@mountsinai.org

(713) 500-7964

Study Officials

• Soren Gantt

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2016
• First Posted: March 13, 2017
• Study Start: March 13, 2017
• Primary Completion: May 23, 2022
• Study Completion: April 13, 2023
• Last Updated: December 17, 2025
• Results First Posted: February 2, 2024

Record last verified: 2025-12

Locations

ZA (1); UG (1); US (10)