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

April 12, 2019 updated by: Abramson Cancer Center of the University of Pennsylvania

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

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4283
        • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum tolerated dose of hydroxychloroquine

Secondary Outcome Measures

Outcome Measure
Response rate
Toxicity rate as assessed by NCI CTCAE v. 3.0
Pharmacokinetic and pharmacodynamic correlative endpoints

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abramson Cancer Center of the University of Pennsylvania

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ravi Amaravadi, MD, Abramson Cancer Center of the University of Pennsylvania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

November 1, 2013

Study Registration Dates

First Submitted

May 28, 2009

First Submitted That Met QC Criteria

May 28, 2009

First Posted (Estimate)

May 29, 2009

Study Record Updates

Last Update Posted (Actual)

April 16, 2019

Last Update Submitted That Met QC Criteria

April 12, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000643294
  • UPCC-08908
  • 807931
  • WYETH-C-UPCC-03809

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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