Study of Whole-brain Irradiation With Chloroquine for Brain Metastases

Study Overview
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Brief Summary
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Background and purposes:Chloroquine (CLQ), an antimalarial drug, has a lysosomatrophic effect associate with increase the sensibility of Radiation through leakage of hidroliticenzimes, increase of apoptosis, autophagy mediated by lysosomalhidrolases and increase of oxidative stress in vitro. In this phase II study we evaluated the efficacy and safety as radiosensitizing of the Chloroquine plus concomitant 30 Gray (Gy) of Whole-brain irradiation (WBI)in patients with brain metastases (BM) from solid tumors.

Detailed Description
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Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ group). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC QLQ-C30 questionnaire (Mexican version) before beginning radiotherapy and one month later.

Official Title
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Phase II Randomized, Double Blind, Placebo Controlled Study of Whole-brain Irradiation With Concomitant Daily-dose Chloroquine for Brain Metastases.

Conditions
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Brain Metastasis

Intervention / Treatment
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* Drug: Chloroquine
* Radiation: Total brain radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 80 years of age At leat one brain metastasis MRI KPS 70 or more RTOG-RPA I or II Basic Laboratory requirements Exclusion Criteria: Candidates for radiosurgery, neurosurgery Patients treated with radiotherapy before entered to the study

Ages Eligible for Study
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Minimum Age: 46 Years
Maximum Age: 61 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroquine, radiosensitizer<br>The patients in the Chloroquine group received 30 Gy of total brain radiotherapy in 10 daily fractions from Monday to Friday. Furthermore, the CLQ plus WBI arm received a daily single dose of 150 mg CLQ po 1 hour prior to the radiation treatment, beginning during the first radiotherapy fraction and continuing for 28 days. | Drug: Chloroquine<br>* The patients in the Chloroquine group received 30 Gy of total brain radiotherapy in 10 daily fractions from Monday to Friday. Furthermore, the Chloroquine plus WBI arm received a daily single dose of 150 mg CLQ po 1 hour prior to the radiation treatment, beginning during the first radiotherapy fraction and continuing for 28 days<br>* Other names: Aralen;Radiation: Total brain radiotherapy<br>* 30 Gy in 10 daily fractions from Monday to Friday<br>|
| Placebo Comparator: Placebo<br>30 Gy of whole-brain radiotherapy in 10 daily fractions and an oral matching placebo for 28 days | Radiation: Total brain radiotherapy<br>* 30 Gy in 10 daily fractions from Monday to Friday<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Corresponding Complete plus Partial Response according with RECIST 1.1 Criteria | Every third month after randomization until 24 months follow-up. Measured by brain MRI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central Nervous System Progression Free Survival | Clinical o radiological brain progression or death. Radiological Progression is measured by RECIST 1.1 Criteria | From time to progression to 24 months follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prophylactic Cranial Irradiation, Metastasis, Cloroquine