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

Completed · Phase 1

Conditions studied: Solid Tumors

In brief

Background: * The PI3K/Akt/mTOR pathway is an important target in cancer because it promotes chemotherapeutic resistance and confers a poor prognosis for many types of cancers. * Several inhibitors of the pathway are being developed as cancer therapeutics. However, the process of de novo drug development takes years, and is often curtailed due to diminished activity and/or unforeseen toxicities in clinical trials. * One approach to expedite the development of new cancer therapies is to test drugs that are already approved for other indications. * Our group has shown that nelfinavir, an orally available FDA-approved HIV-1 protease inhibitor used to treat HIV/AIDS, can inhibit endogenous Akt and growth factor receptor induced Akt activity in cancer cells. * Importantly, nelfinavir demonstrates dose-dependent cytotoxicity in every cell line in the NCI 60 cell line panel at plasma concentrations attainable in human plasma, is profoundly effective in cancer cell lines that have been selected to become resistant to standard therapies, and inhibits tumor growth in-vivo. Objectives: * Because an MTD with nelfinavir has not been observed in prior phase I studies with HIV patients, the objectives of the Phase I design will be: * To establish the MTD and dose limiting toxicity for this drug in patients with solid Tumors. * To correlate nelfinavir pharmacokinetics with baseline activity of CYP3A4 as assessed by measuring midazolam clearance. * To preliminarily explore the biological and clinical effects through a series of correlative studies involving analysis of blood and tissue across patients throughout the study. Eligibility: -Adults with solid tumors who are refractory to, or have relapsed after receiving, standard front-line chemotherapies are eligible. Design: * Patients will receive nelfinavir beginning at the FDA-approved dose for HIV patients (1250 mg po bid). * Dose escalations will occur for 6 dose levels i.e. cohorts, or until the MTD is reached. * Up to 45 patients are expected to be enrolled. * Staging CT scans will be performed every two cycles.

Key facts

Study ID

NCT01445106

Run by

National Cancer Institute (NCI)

People needed

28

Starts

2006-12-11

Expected to finish

2011-05-09

Last updated by the study team

2019-12-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• 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.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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