Hydroxychloroquine and Temsirolimus in Treating Patients With Metastatic Solid Tumors That Have Not Responded to Treatment
Recruitment status was Recruiting
RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with temsirolimus may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of hydroxychloroquine when given together with temsirolimus in treating patients with metastatic solid tumors that have not responded to treatment.
Unspecified Adult Solid Tumor, Protocol Specific
Other: electron microscopy
Other: high performance liquid chromatography
Other: immunologic technique
Other: laboratory biomarker analysis
Other: mass spectrometry
Other: pharmacological study
Procedure: autophagy inhibition therapy
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase I Trial of Hydroxychloroquine in Combination With Temsirolimus in Patients With Refractory Solid Tumors|
- Maximum tolerated dose of hydroxychloroquine [ Designated as safety issue: Yes ]
- Response rate [ Designated as safety issue: No ]
- Toxicity rate as assessed by NCI CTCAE v. 3.0 [ Designated as safety issue: Yes ]
- Pharmacokinetic and pharmacodynamic correlative endpoints [ Designated as safety issue: No ]
|Study Start Date:||October 2008|
|Estimated Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
- 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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00909831
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|Contact: Clinical Trials Office - Abramson Cancer Center of the Univers 800-474-9892|
|Principal Investigator:||Ravi Amaravadi, MD||Abramson Cancer Center of the University of Pennsylvania|