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

Phase 1
18 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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



- 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.

Inclusion Criteria


- 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

- 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

- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of hydroxychloroquine

Safety Issue:


Principal Investigator

Ravi Amaravadi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania



Study ID:




Start Date:

October 2008

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms



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