Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas

Study Overview
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Brief Summary
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The purpose of this study is to preliminarily evaluate the safety and efficacy of cabergoline combined hydroxychloroquine/chloroquine(HCQ/CQ) therapy for cabergoline-Resistant Prolactinomas

Detailed Description
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The dopamine agonist cabergoline (CAB) has been used widely in the treatment of prolactinomas, but its clinical use is hampered by intolerance and/or resistant in some patients with prolactinoma. Chloroquine (CQ) is an old drug widely used to treat malaria. Recent studies, including our own (J Clin Endocrinol Metab, 2017; Autophagy, 2017; Oncotarget, 2015), have revealed that CAB and CQ are involved in induction of autophagy and activation of autophagic cell death. Furthermore, CQ enhanced suppression of cell proliferation by CAB. We established a low-CAB-dose condition in which CAB was able to induce autophagy but failed to suppress cell growth. Addition of CQ to low-dose CAB blocked normal autophagic cycles and induced apoptosis, evidenced by the further accumulation of p62/caspase-8/LC3-II. The data suggest that combined use of CAB and CQ may increase clinical effectiveness in treatment of intolerance and/or resistant prolactinomas.

Official Title
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The Effect of Combined Treatment of Cabergoline With Hydroxychloroquine/Chloroquine for Resistant Prolactinomas

Conditions
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Resistance, Disease, Prolactinoma

Intervention / Treatment
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* Drug: HCQ/CQ and CAB combined treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 70 years old, either sex; Karnofsky performance status ≥ 70; Patients who were suffered drug-resistant,which has taken cabergoline ≥2.0mg/week no less than 3 months, referring to failure to normalize PRL levels and failure to decrease macroprolactinoma size by >or=50%; The patient has signed the informed consent. Exclusion Criteria: Patients concomitantly taking the psychotropic drugs or other drugs causing elevated PRL ; Patients with parkinson disease and is taking dopaminergic agents; Patients with prolactinoma who received Gamma knife treatment; Patients who use any dopamine receptor agonists other than cabergoline; pregnant or lactating women, or women preparing pregnant; Patients with poor compliance, who cannot implement the program strictly. History of allergic reactions attributed to compounds of similar chemical or biologic composition to HCQ. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, as HCQ may cause hemolytic anemia in patients with G6PD deficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: HCQ/CQ and CAB combined treatment<br>Subjects are treated with hydroxychloroquine sulfate tablets 5mg/kg Bid and cabergoline tablets 2mg/week for 3 months. | Drug: HCQ/CQ and CAB combined treatment<br>* Subjects are treated with hydroxychloroquine sulfate tablets 5mg/kg Bid and cabergoline tablets 2mg/week for 3 months.After therapy of 3 months the medication will be stopped if does not reduce prl level more than 20% or failure to decrease prolactinoma size.<br>* Other names: HCCT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline on prolactin(PRL) level | Record the result of prolactin on every 3 month follow-up visit | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline on tumor volume measured by enhanced pituitary Magnetic Resonance Imaging（MRI） | Record the tumor volume from enhanced pituitary MRI on every 3 month follow-up visits | Up to 6 months | 
| Change from baseline of visual acuity | Record the Visual acuity on every 3 month follow-up visit | Up to 6 months | 
| Change from baseline on 5 point visual field scale | Record the Visual field scale on every 3 month follow-up visit, 0 = normal, no vision loss; 1 = one quadrant vision loss; 2 = two quadrants of vision loss; 3 = three quadrants of vision loss; 4 = four quadrants of vision loss but retain a central tubular vision; 5 = blind | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cabergoline, prolactinomas, resistant, hydroxychloroquine, chloroquine