NCT00909831

Hydroxychloroquine and Temsirolimus in Treating Patients With Metastatic Solid Tumors That Have Not Responded to Treatment

A Phase I Trial of Hydroxychloroquine in Combination With Temsirolimus in Patients With Refractory Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Abramson Cancer Center at Penn Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
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

Timeline

• Start date: 2008-10-01
• Primary completion: 2012-05-01
• Completion: 2013-11-01
• First posted: 2009-05-29
• Last updated: 2019-04-16

Locations

1 site across 1 country: United States