Nelfinavir Mesylate in Treating Patients With Kaposi Sarcoma

Exclusion Criteria

• •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:
• •Glucocorticoids: cortisone (\> 50 mg), hydrocortisone (\> 40 mg), prednisone (\> 10 mg), methylprednisolone (\> 8 mg), dexamethasone (\> 1.5 mg)
• •Anticonvulsants: phenytoin, carbamazepine, primidone, phenobarbital and other enzyme inducing anti-convulsant drugs (EIACD)
• •Antibiotics: rifampin (rifampicin), rifabutin, rifapentine
• •Miscellaneous: St. John's Wort, modafinil
• •Strong Inhibitors of CYP2C9:
• •Antifungals: fluconazole; lists including medications and substances known or with the potential to interact with the CYP3A or 2C19
• •Drugs with KSHV antiviral activity:
• •Participants receiving any medications or substances that may interfere with KSHV replication are ineligible Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; medical reference texts such as the physicians' desk reference may also provide this information; as part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product; lists include medications and substances known or with the potential to interfere with KSHV replication
• •* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• •* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with high dose nelfinavir
• •* Chronic diarrhea as defined by loose or watery stools occurring more than 3 times daily at baseline lasting more than 4 weeks or not abating on condition-appropriate therapy prior to study enrollment
• •* Participant is \< 2 years free of another primary malignancy; exceptions include basal cell skin cancer, stage 0-I squamous cell cancer of the skin, cervical carcinoma in situ, anal carcinoma in situ
• •* Use of systemic corticosteroid therapy (except for replacement doses of glucocorticoid and/or mineralocorticoid for adrenal insufficiency); inhaled or intranasal corticosteroids for allergic or bronchospastic conditions are permitted