Clinical trial NCT03400865: Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas
Official title: The Effect of Combined Treatment of Cabergoline With Hydroxychloroquine/Chloroquine for Resistant Prolactinomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Resistance, Disease
Prolactinoma
Keywords: cabergoline
prolactinomas
resistant
hydroxychloroquine
chloroquine
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Xinqiao Hospital of Chongqing
name: First Hospital of China Medical University
name: Beijing Tiantan Hospital
name: First Affiliated Hospital of Wenzhou Medical University
name: First Affiliated Hospital of Fujian Medical University
name: Peking Union Medical College Hospital
name: Huashan Hospital
name: Chinese PLA General Hospital
First posted: 2018-01-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline on prolactin(PRL) level
timeFrame: Up to 6 months
Secondary outcomes:
measure: Change from baseline on tumor volume measured by enhanced pituitary Magnetic Resonance Imaging（MRI）
timeFrame: Up to 6 months
measure: Change from baseline of visual acuity
timeFrame: Up to 6 months
measure: Change from baseline on 5 point visual field scale
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hosipital
state: Shanghai
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Chongqing
country: China
facility: Xinqiao Hospital of Chongqing
city: Fujian
country: China
facility: First Affiliated Hospital of Fujian Medical
city: Shenyang
country: China
facility: First Hospital of China Medical University
city: Wenzhou
country: China
facility: First Affiliated Hospital of Wenzhou Medical Univeristy
Study officials:
affiliation: Ruijin Hospital
name: Zhebao Wu, Medical
role: STUDY_CHAIR
References:
citation: Leng ZG, Lin SJ, Wu ZR, Guo YH, Cai L, Shang HB, Tang H, Xue YJ, Lou MQ, Zhao W, Le WD, Zhao WG, Zhang X, Wu ZB. Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death. Autophagy. 2017 Aug 3;13(8):1404-1419. doi: 10.1080/15548627.2017.1328347. Epub 2017 Jun 14.
citation: Lin SJ, Leng ZG, Guo YH, Cai L, Cai Y, Li N, Shang HB, Le WD, Zhao WG, Wu ZB. Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline. Oncotarget. 2015 Nov 17;6(36):39329-41. doi: 10.18632/oncotarget.5744.
citation: Lin SJ, Wu ZR, Cao L, Zhang Y, Leng ZG, Guo YH, Shang HB, Zhao WG, Zhang X, Wu ZB. Pituitary Tumor Suppression by Combination of Cabergoline and Chloroquine. J Clin Endocrinol Metab. 2017 Oct 1;102(10):3692-3703. doi: 10.1210/jc.2017-00627.