A Phase I Trial of Nelfinavir (Viracept) in Adults With Solid Tumors
-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.
-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
-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
-Adults with solid tumors who are refractory to, or have relapsed after receiving, standard
front-line chemotherapies are eligible.
- 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
- Up to 45 patients are expected to be enrolled.
- Staging CT scans will be performed every two cycles.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
To determine the safety and toxicity of nelfinavir in human subjects with solid tumors and to determine the maximum tolerated dose in this group of patients.
Arun Rajan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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