A Phase I Trial of Nelfinavir (Viracept ) in Adults With Solid Tumors

• INCLUSION CRITERIA:

Patients must have a histologically confirmed solid malignancy by the Laboratory of Pathology at the Clinical Center/NIH or the Laboratory of Pathology at NNMC.

Patients must: have either relapsed following, or progressed through, standard therapy; have a current disease state for which there is no standard effective therapy; have refused standard therapy in cases where no curative option exists.

Patients may have had any number of chemotherapeutic regimens.

Age greater than or equal to 18 years of age.

ECOG performance score of less than or equal to 2.

An expected survival of greater than or equal to 3 months.

Patients must have the capacity and willingness to sign a written informed consent and demonstrate willingness to comply with an oral regimen.

Patients must have normal organ and marrow function as defined below:

• absolute neutrophil count greater than or equal to 1,500/mL.
• platelets greater than or equal to 100,000/mL.
• total bilirubin less than 1.5 X upper limit of institutional normal.
• AST(SGOT) less than or equal to 2.5 X upper limit of institutional normal.
• ALT(SGPT) less than or equal to 2.5 X upper limit of institutional normal.
• Creatinine less than 1.5 X upper limit of institutional normal.

Patients must agree to use non-hormonal methods of birth control, e.g., barrier methods, for the duration of the study due to possible drug interactions.

Patients will be asked if they would consent to a biopsy before and after treatment in order to provide biologic correlates for analysis, but these will be optional, and the patients will be eligible whether they consent to do this or not.

Patients with brain metastasis must have undergone evaluation and appropriate counseling and treatment by radiation oncology.

EXCLUSION CRITERIA:

Pregnant or lactating women.

Patients who have had chemotherapy or biologic agents in the last 28 days prior to entering the study.

Any concurrent therapy with chemotherapeutic agents or biologic agents or radiation therapy.

Patients with a myocardial infarction in the six months prior to enrollment.

Patients with 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.

Patients that are on the following CYP3A4 inhibitors and cannot replace these medications with other equivalent medications for the period of the study: antiarrhythmics (amiodarone, quinidine), neuroleptics (pimozide), sedative/hypnotic agents (midazolam, triazolam), ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), HMG-CoA reductase inhibitors (lovastatin, simvastatin, atorvastatin), rifampin, rifabutin, felodipine, nifedipine, and sildenafil or St. John's wort. Patients whose baseline medication regimen includes 2 or more medications of a class carries the potential for serious side effects, and which must be changed becaused of potential interaction with nelfinavir, they must be stable on the new regimen for 7 days before enrollment.

Patients that are on escalating doses of corticosteroids for other non-cancerous medical conditions.