Hydroxychloroquine in Treating Patients With Solid Tumors Undergoing Radiation Therapy for Bone Metastases

OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of hydroxychloroquine that can safely be
administered to cancer patients in association with radiation prior to developing this
approach for disease treatment.

OUTLINE: This is a dose escalation study.

Beginning 3 days before the initiation of radiotherapy, patients receive hydroxychloroquine
orally (PO) once daily (QD) or twice daily (BID). Treatment continues until completion of
radiotherapy.

After completion of study treatment, patients are followed up at 4 weeks.

Inclusion Criteria:

- Patients must have a histologically confirmed solid tumor with radiographic evidence
of bony metastatic disease and symptoms requiring palliative radiotherapy

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Life expectancy of greater than 6 weeks

- Leukocytes >= 3,000/uL

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin =< 1.5 X institutional upper limit of normal

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT])
=<2.5 X institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with calculated creatinine levels above institutional
normal limits

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy within 4 weeks prior to entering the study or
those who have not recovered from acute adverse events due to agents administered
more than 4 weeks earlier

- Patients may not have received prior radiotherapy to the intended site

- Patients who have not recovered from acute adverse events due to previous
radiotherapy

- Patients may not be receiving any other investigational agents

- Patients who are neurologically unstable due to uncontrolled brain metastases are
excluded from this clinical trial because of their poor prognosis and because they
often develop progressive neurologic dysfunction that would confound the evaluation
of neurologic and other adverse events. - - History of allergic reactions
attributed to compounds of similar chemical or biologic composition to
hydroxychloroquine

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Patients who are pregnant or may become pregnant during treatment

- Patients with severe psoriasis who may experience a flare of disease with
hydroxychloroquine use

- Patients with known liver dysfunction (elevated transaminases or abnormal coagulation
studies); patients with metastatic disease to the liver with normal liver function
studies may be enrolled

- Patients with retinopathy