A Phase I Trial of Nelfinavir (Viracept ) in Adults With Solid Tumors
|First Received Date ICMJE||September 30, 2011|
|Last Updated Date||November 27, 2013|
|Start Date ICMJE||December 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||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.|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01445106 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||To determine the PK of nelfinavir admin, correlate cytochrome P450 3A4 activity with nelfinavir levels and establish prelim evidence of clinical efficacy of this regimen in solid tumor malignancy patients.|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||A Phase I Trial of Nelfinavir (Viracept ) in Adults With Solid Tumors|
|Official Title ICMJE||A Phase I Trial of Nelfinavir (Viracept) in Adults With Solid Tumors|
-Adults with solid tumors who are refractory to, or have relapsed after receiving, standard front-line chemotherapies are eligible.
-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.
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Solid Tumors|
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||May 2011|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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:
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.
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.
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01445106|
|Other Study ID Numbers ICMJE||070047, 07-C-0047|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||January 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP