Hydroxychloroquine and Temsirolimus in Treating Patients With Metastatic Solid Tumors That Have Not Responded to Treatment
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00909831|
Recruitment Status : Completed
First Posted : May 29, 2009
Last Update Posted : April 16, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: hydroxychloroquine Drug: temsirolimus 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||Phase 1|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Official Title:||A Phase I Trial of Hydroxychloroquine in Combination With Temsirolimus in Patients With Refractory Solid Tumors|
|Study Start Date :||October 2008|
|Actual Primary Completion Date :||May 2012|
|Actual Study Completion Date :||November 2013|
- Maximum tolerated dose of hydroxychloroquine
- Response rate
- Toxicity rate as assessed by NCI CTCAE v. 3.0
- Pharmacokinetic and pharmacodynamic correlative endpoints
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00909831
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|Principal Investigator:||Ravi Amaravadi, MD||Abramson Cancer Center of the University of Pennsylvania|