Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas

Prolactinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03400865
• Other study ID #: HCCT-2018
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 25, 2018
• Est. completion date: December 30, 2020

Study information

• Verified date: January 2018
• Source: Ruijin Hospital
• Contact: Shaojian Lin, MD
• Phone: 0086-15801782758
• Email: shaojianlin88[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 30, 2020
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Prolactinoma
• Resistance, Disease

Intervention

Drug:
• HCQ/CQ and CAB combined treatment
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.

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Xinqiao Hospital of Chongqing	Chongqing
China	First Affiliated Hospital of Fujian Medical	Fujian
China	Huashan Hospital	Shanghai	Shanghai
China	Ruijin Hosipital	Shanghai	Shanghai
China	First Hospital of China Medical University	Shenyang
China	First Affiliated Hospital of Wenzhou Medical Univeristy	Wenzhou

Sponsors (9)

Lead Sponsor	Collaborator
Zhebao Wu	Beijing Tiantan Hospital, Chinese PLA General Hospital, First Affiliated Hospital of Fujian Medical University, First Affiliated Hospital of Wenzhou Medical Univeristy, First Hospital of China Medical University, Huashan Hospital, Peking Union Medical College Hospital, Xinqiao Hospital of Chongqing

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline on prolactin(PRL) level	Record the result of prolactin on every 3 month follow-up visit	Up to 6 months
Secondary	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
Secondary	Change from baseline of visual acuity	Record the Visual acuity on every 3 month follow-up visit	Up to 6 months
Secondary	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