A Phase I Trial of Hydroxychloroquine in Combination With Temsirolimus in Patients With Refractory Solid Tumors
- Determine the maximum tolerated dose of hydroxychloroquine (HCQ) in combination with
temsirolimus (TEM) in patients with metastatic refractory solid tumors.
- Describe the toxicity of this regimen in these patients.
- Measure the response rate in patients treated with this regimen.
- 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
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.
Primary Purpose: Treatment
Maximum tolerated dose of hydroxychloroquine
Ravi Amaravadi, MD
Abramson Cancer Center of the University of Pennsylvania
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|