Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas

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

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

Study Overview

• Status: Unknown
• Conditions: Resistance, Disease; Prolactinoma
• Intervention / Treatment: Drug: HCQ/CQ and CAB combined treatment

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhebao Wu, Medical PhD; Phone Number: 0086-021-64370045; Email: zhebaowu@aliyun.com
• Study Contact Backup: Name: Shaojian Lin, MD; Phone Number: 0086-15801782758; Email: shaojianlin88@126.com

Study Locations

• China
  • Beijing, China
    • Chinese PLA General Hospital
  • Beijing, China
    • Peking Union Medical College Hospital
  • Chongqing, China
    • Xinqiao Hospital of Chongqing
  • Fujian, China
    • First Affiliated Hospital of Fujian Medical
  • Shenyang, China
    • First Hospital of China Medical University
  • Wenzhou, China
    • First Affiliated Hospital of Wenzhou Medical Univeristy
  • Beijing
    • Beijing, Beijing, China
      • Beijing Tiantan Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Huashan Hospital
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hosipital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HCQ/CQ and CAB combined treatment; 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; 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.; Other Names: HCCT

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zhebao Wu
• Collaborators: Peking Union Medical College Hospital; Beijing Tiantan Hospital; Chinese PLA General Hospital; Huashan Hospital; First Affiliated Hospital of Fujian Medical University; Xinqiao Hospital of Chongqing; First Hospital of China Medical University; First Affiliated Hospital of Wenzhou Medical University
• Investigators: Study Chair: Zhebao Wu, Medical, Ruijin Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 25, 2018
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 14, 2018
• First Posted (Actual): January 17, 2018

Study Record Updates

• Last Update Posted (Actual): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 14, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: hydroxychloroquine; resistant; chloroquine; cabergoline; prolactinomas
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Disease Attributes; Endocrine Gland Neoplasms; Hypothalamic Diseases; Pituitary Diseases; Adenoma; Pituitary Neoplasms; Disease Resistance; Prolactinoma
• Other Study ID Numbers: HCCT-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: The individual patient Data would not be shared to the third facility, but the sponsor hasn't decided whether to share the individual patient date to the other related studies hold by himself in the future.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No