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

A Phase 1 Study of Hydroxychloroquine in Patients With Solid Tumors Receiving Radiotherapy for Bone Metastases

This phase I trial studies the side effects and best dose of hydroxychloroquine in treating patients with solid tumors undergoing radiation therapy for bone metastases. Drugs, such as hydroxychloroquine, may make tumor cells more sensitive to radiation therapy

Study Overview

• Status: Terminated
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Bone Metastases
• Intervention / Treatment: Radiation: radiation therapy; Drug: hydroxychloroquine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment (radiosensitization therapy); Beginning 3 days before the initiation of radiotherapy, patients receive hydroxychloroquine PO QD or BID. Treatment continues until completion of radiotherapy.	Radiation: radiation therapy; Undergo radiotherapy; Other Names: irradiation; radiotherapy; therapy, radiation; Drug: hydroxychloroquine; Given PO; Other Names: HCQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD of hydroxychloroquine that can be safely administered to cancer patients in association with radiotherapy	Safety assessments weekly during treatment and at 4 weeks post-radiotherapy	12 weeks

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Laurie Cuttino, Massey Cancer Center

Publications and helpful links

Helpful Links

• VCU Massey Cancer Center

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: August 10, 2011
• First Submitted That Met QC Criteria: August 15, 2011
• First Posted (ESTIMATE): August 16, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 3, 2015
• Last Update Submitted That Met QC Criteria: February 1, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Hematologic Diseases; Musculoskeletal Diseases; Neoplastic Processes; Bone Diseases; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: MCC-13713; P30CA016059 (U.S. NIH Grant/Contract); NCI-2011-02310 (REGISTRY: CTRP (Clinical Trial Reporting Program))