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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. Identifier: NCT00909831
Recruitment Status : Completed
First Posted : May 29, 2009
Last Update Posted : April 16, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

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.

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

Detailed Description:



  • 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Maximum tolerated dose of hydroxychloroquine

Secondary Outcome Measures :
  1. Response rate
  2. Toxicity rate as assessed by NCI CTCAE v. 3.0
  3. Pharmacokinetic and pharmacodynamic correlative endpoints

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed refractory solid tumor for which no curative standard therapy exists

    • Metastatic disease
  • Treated brain metastases that have been stable ≥ 3 months allowed

    • At least 1 week since prior steroids


  • ECOG performance status of 0-1
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 2 times upper limit of normal (ULN)
  • ALT and AST ≤ 5 times ULN
  • Total bilirubin ≤ 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious concurrent infection or medical illness that would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
  • No prior or other concurrent malignancy except for curatively treated carcinoma-in-situ at any site or basal cell carcinoma or squamous cell carcinoma of the skin

    • Patients who have been free of disease (any prior malignancy) for ≥ 5 years are eligible
  • 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


  • 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

Information from the National Library of Medicine

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 identifier (NCT number): NCT00909831

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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
National Cancer Institute (NCI)
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Principal Investigator: Ravi Amaravadi, MD Abramson Cancer Center of the University of Pennsylvania
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Responsible Party: Abramson Cancer Center of the University of Pennsylvania Identifier: NCT00909831    
Other Study ID Numbers: CDR0000643294
First Posted: May 29, 2009    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
unspecified adult solid tumor, protocol specific
Additional relevant MeSH terms:
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Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Anti-Bacterial Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs