Finding studies
Finding studies
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Lead
Abramson Cancer Center at Penn Medicine
With
OBJECTIVES: Primary * Determine the maximum tolerated dose of hydroxychloroquine (HCQ) in combination with temsirolimus (TEM) in patients with metastatic refractory solid tumors. Secondary * Describe the toxicity of this regimen in these patients. * Measure the response rate in patients treated with this regimen. Tertiary * Establish a population pharmacokinetic (PK) model for HCQ and its metabolites in combination with TEM. * Use the population PK model to estimate the exposure of HCQ in individual patients. * Compare PK parameters for this regimen to data from published single agent studies. * Measure the change in median number of autophagic vesicles/cell in peripheral blood mononuclear cells with TEM alone and with TEM and HCQ and correlate these changes with HCQ exposure. OUTLINE: This is a dose-escalation study of hydroxychloroquine. Patients receive temsirolimus IV over 30 minutes once a week beginning in week 1 and oral hydroxychloroquine twice daily beginning in week 2. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and periodically during study for pharmacokinetic and pharmacodynamic studies and measurement of autophagy inhibition. Samples are analyzed via HPLC and tandem mass spectrometry, immunoblotting assays, and electron microscopy.
Age
18–120
Sex
ALL
Healthy volunteers
Not accepted
