IDO2 Genetic Status Informs the Neoadjuvant Efficacy of Chloroquine (CQ) in Brain Metastasis Radiotherapy

Main Line Health

Status: Completed

Conditions: Brain Metastasis

Treatments: Drug: Chloroquine diphosphate

Study type: Interventional

Funder types: Other

Identifiers

NCT01727531

R09-2775L

Details and patient eligibility

About

This research is being done to determine if a short course of Chloroquine (five weeks) before, during and after whole brain radiation therapy (WBRT) will improve the overall survival of subjects being treated for brain metastases.

Full description

Hypothesis one: A short course of chloroquine one week prior and four weeks after initiation of WBRT is tolerable and significantly increases the median survival time of patients suffering from brain metastasis as assessed one, three, six, nine, twelve and 24 months post radiotherapy, when compared to historic controls.

Hypothesis two: The presence of one or both single-nucleotide polymorphisms (SNP)s in the gene coding for the immunoregulatory enzyme indoleamine 2,3-dioxygenase 2 (IDO2) improves the clinical outcomes of WBRT or the response to CQ co-treatment.

3.2. Specific Aims:

The specific aims of this study are:

1. Determine patients physical profiles prior WBRT and at regular intervals afterwards up to 24 months after radiotherapy.
2. Record the status of patient metastases (i.e. number, location, size)
3. Determine patients' KPS values.
4. Record the incidence and causes of mortality of patients.
5. Determine the genotype of IDO2 for each patient.
6. Following data analysis, test the validity of the two hypotheses.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with histologically confirmed primary solid malignancy
• Patients with single or multiple brain metastases
• Patients with metastasis diameter < 5 cm
• Age > 18
• Clearance from the patient's physician that treatment with chloroquine should not pose a problem to the patient

Exclusion criteria

• Patients with a history of hypotension, cardiomyopathy, epilepsy, seizures
• Patients with impaired renal function
• Patients with psoriasis, porphyria
• Patients with known hypersensitivity to 4-aminoquinoline compounds
• Pregnancy, nursing
• Prior radiotherapy
• During the chloroquine treatment, patients complaining from visual or auditory disturbances, and patients suffering from acute gastrointestinal problems i.e. Anorexia, nausea, vomiting, diarrhea, abdominal cramps

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

CQ Arm

Experimental group

Description:

250 mg chloroquine once a day by mouth beginning one week prior to beginning radiation therapy and continue for a total of five weeks.

Treatment:

Drug: Chloroquine diphosphate