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

NCT ID: NCT00909831

Last Updated: 2019-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2013-11-30

Brief 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

Study Design

• Primary Study Purpose: TREATMENT

Interventions

hydroxychloroquine

Intervention Type: DRUG

temsirolimus

Intervention Type: DRUG

electron microscopy

Intervention Type: OTHER

high performance liquid chromatography

Intervention Type: OTHER

immunologic technique

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

mass spectrometry

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

autophagy inhibition therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• No porphyria
• No psoriasis, except well controlled psoriasis under the care of a specialist
• No previously documented macular degeneration or diabetic retinopathy
• No HIV positivity

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Any number and type of prior anticancer therapies allowed
• No prior mTOR inhibitors
• At least 4 weeks since prior immunotherapy (i.e., aldesleukin, interferon, CTLA-4) or chemotherapy and recovered
• At least 2 weeks since prior oral targeted therapy and recovered
• At least 4 weeks since prior and no other concurrent investigational anticancer therapy (except for vaccines)
• No other concurrent therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent cytochrome P450 enzyme-inducing anticonvulsant drugs (i.e., phenytoin, carbamazepine, phenobarbital, primidone, or oxcarbazepine)
• Concurrent non-enzyme inducing anticonvulsants, including felbamate, valproic acid, gabapentin, lamotrigine, tiagabine, topiramate, zonisamide, or levetiracetam allowed
• Concurrent hematologic growth factors (filgrastim [G-CSF], pegfilgrastim, epoetin alfa) allowed in patients with severe myelosuppression

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ravi Amaravadi, MD

Role: PRINCIPAL_INVESTIGATOR

Abramson Cancer Center at Penn Medicine

Locations

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

UPCC-08908

Identifier Type: -

Identifier Source: secondary_id

807931

Identifier Type: -

Identifier Source: secondary_id

WYETH-C-UPCC-03809

Identifier Type: -

Identifier Source: secondary_id

CDR0000643294

Identifier Type: -

Identifier Source: org_study_id