Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas

Not Applicable

• Conditions: Prolactinoma; Resistance, Disease
• Interventions: Drug: HCQ/CQ and CAB combined treatment

• Registration Number: NCT03400865
• Lead Sponsor: Zhebao Wu

Brief Summary

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

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 Timeline

• Status Verified: 2018-01
• Study First Submitted: 2018-01-08
• Study First Submitted QC: 2018-01-14
• Study First Posted: 2018-01-17
• Last Update Submitted: 2018-10-14
• Last Update Posted: 2018-10-16
• Study Start: 2018-10-25
• Primary Completion: 2020-12-30
• Study Completion: 2020-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HCQ/CQ and CAB combined treatment	HCQ/CQ and CAB combined treatment	Subjects are treated with hydroxychloroquine sulfate tablets 5mg/kg Bid and cabergoline tablets 2mg/week for 3 months.

Primary Outcome Measures

Name	Time	Method
Change from baseline on prolactin(PRL) level	Up to 6 months	Record the result of prolactin on every 3 month follow-up visit

Secondary Outcome Measures

Name	Time	Method
Change from baseline of visual acuity	Up to 6 months	Record the Visual acuity on every 3 month follow-up visit
Change from baseline on tumor volume measured by enhanced pituitary Magnetic Resonance Imaging（MRI）	Up to 6 months	Record the tumor volume from enhanced pituitary MRI on every 3 month follow-up visits
Change from baseline on 5 point visual field scale	Up to 6 months	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

Trial Locations

Locations (9)

Huashan Hospital; 🇨🇳 Shanghai, Shanghai, China

Ruijin Hosipital; 🇨🇳 Shanghai, Shanghai, China

Xinqiao Hospital of Chongqing; 🇨🇳 Chongqing, China

First Affiliated Hospital of Fujian Medical; 🇨🇳 Fujian, China

First Hospital of China Medical University; 🇨🇳 Shenyang, China

First Affiliated Hospital of Wenzhou Medical Univeristy; 🇨🇳 Wenzhou, China

Beijing Tiantan Hospital; 🇨🇳 Beijing, Beijing, China

Chinese PLA General Hospital; 🇨🇳 Beijing, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, China