Study of Nelfinavir and Temsirolimus in Patients With Advanced Cancers

• Status: Completed
• Trial end date: 2011-08-01
• Target enrollment: 0
• Participant gender: All

Summary

In the present study the investigators want to explore the safety, pharmacokinetics, and activity of the combination of temsirolimus and nelfinavir, both agents with PI3K /Akt/mTOR inhibiting activity, in patients with advanced malignancies.Temsirolimus has proven anti tumoral activity by mTOR inhibition. Nelfinavir is a potential inhibitor of Akt. Combining both agents might prevent upregulation of the P13k pathway and increase the anti-cancer activity of temsirolimus. The strong CYP3A4 inhibition of nelfinavir and the dependence of temsirolimus on CYP3 A4 metabolism makes a dose finding study essential. The investigators will also look at the prospective value of biomarkers of activity and the outcome of the treatment.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Treatments: Everolimus; Nelfinavir; Sirolimus

Criteria

Inclusion Criteria:

• Patients with histological or cytological confirmed malignancies

• ECOG / WHO performance status of 0-2

• Age 18 years

• Life expectancy of at least 3 months

• Minimal acceptable safety laboratory values defined as

• WBC 3.0 x 109 /L

• Platelet count 100 x 109 /L

• Hepatic function as defined by serum bilirubin 1.5 x ULN, ALT or AST 2.5 x ULN, in case of liver metastases 5 x ULN

• Renal function as defined by creatinine < 150μmol/L

• Able and willing to give written informed consent according to ICH/GCP, and national/local regulations.

• Able to swallow and retain oral medication

• Able and willing to undergo blood sampling for pharmacokinetic and pharmacogenetic analysis

• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Exclusion Criteria:

• Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up

• Women who are pregnant or breast feeding

• Women of childbearing potential who refuse to use a reliable contraceptive method throughout the study

• Serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator

• Any other medical condition that would interfere with study procedures and/or decrease safety of the protocol treatment

• Concomitant use of strong CYP3A4 inhibitors, CYP3A4 inducers or CYP substrates