Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas

Zhebao Wu30 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Resistance, Disease Prolactinoma

Interventions

HCQ/CQ and CAB combined treatmentDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Aged between 18 and 70 years old, either sex; 2. Karnofsky performance status ≥ 70; 3. 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%; 4. The patient has signed the informed consent. Exclusion Criteria: 1. Patients concomitantly taking the psychotropic drugs or other drugs causing elevated PRL ; 2. Patients with parkinson disease and is taking dopaminergic agents; 3. Patients with prolactinoma who received Gamma knife treatment; 4. Patients who use any dopamine receptor agonists other than cabergoline; 5. pregnant or lactating women, or women preparing pregnant; 6. Patients with poor compliance, who cannot implement the program strictly. 7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to HCQ. 8. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, as HCQ may cause hemolytic anemia in patients with G6PD deficiency.

Locations (9)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, China

Huashan Hospital

Shanghai, Shanghai Municipality, China

Ruijin Hosipital

Shanghai, Shanghai Municipality, China

Chinese PLA General Hospital

Beijing, China

Outcomes

Primary Outcomes

Change from baseline on prolactin(PRL) level

Record the result of prolactin on every 3 month follow-up visit

Time frame: Up to 6 months

Secondary Outcomes

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

Time frame: Up to 6 months

Change from baseline of visual acuity

Record the Visual acuity on every 3 month follow-up visit

Time frame: 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

Time frame: Up to 6 months

Central Contacts

Shaojian Lin, MD

CONTACT

0086-15801782758 shaojianlin88@126.com

Zhebao Wu, Medical PhD

CONTACT

0086-021-64370045 zhebaowu@aliyun.com

Data from ClinicalTrials.gov

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