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

Study Overview
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Brief Summary
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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.

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

Official Title
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IDO2 Genetic Status Informs the Neoadjuvant Efficacy of Chloroquine in Brain Metastasis Radiotherapy.

Conditions
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Brain Metastasis

Intervention / Treatment
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* Drug: Chloroquine diphosphate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CQ Arm<br>250 mg chloroquine once a day by mouth beginning one week prior to beginning radiation therapy and continue for a total of five weeks. | Drug: Chloroquine diphosphate<br>* 250 mg chloroquine once a day by mouth beginning one week prior to beginning radiation therapy and continue for a total of five weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specific Aim | Determine patients physical profiles prior WBRT and at regular intervals afterwards up to 24 months after radiotherapy | up to 24-months after completion of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoint: death | from any cause | up to 24 months after completion of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chloroquine, WBRT, survival, brain metastasis, radiotherapy, SNPs, gene coding, immunoregulatory enzyme IDO2