Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas

NCT ID: NCT03400865

Last Updated: 2018-10-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-25
• Study Completion Date: 2020-12-30

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.

Conditions

Resistance, Disease; Prolactinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HCQ/CQ and CAB combined treatment

Subjects are treated with hydroxychloroquine sulfate tablets 5mg/kg Bid and cabergoline tablets 2mg/week for 3 months.

Group Type: EXPERIMENTAL

HCQ/CQ and CAB combined treatment

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

HCCT

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xinqiao Hospital of Chongqing

OTHER

Sponsor Role: collaborator

First Hospital of China Medical University

OTHER

Sponsor Role: collaborator

Beijing Tiantan Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Fujian Medical University

OTHER

Sponsor Role: collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role: collaborator

Huashan Hospital

OTHER

Sponsor Role: collaborator

Chinese PLA General Hospital

OTHER

Sponsor Role: collaborator

Zhebao Wu

OTHER

Sponsor Role: lead

Responsible Party

Zhebao Wu

Chief Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Zhebao Wu, Medical

Role: STUDY_CHAIR

Ruijin Hospital

Locations

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

Peking Union Medical College Hospital

Beijing, , 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

Countries

China

Central Contacts

Shaojian Lin, MD

Role: CONTACT

shaojianlin88@126.com

0086-15801782758

Zhebao Wu, Medical PhD

Role: CONTACT

zhebaowu@aliyun.com

0086-021-64370045

References

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.

Reference Type: BACKGROUND

PMID: 28613975 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26513171 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28973192 (View on PubMed)

Other Identifiers

HCCT-2018

Identifier Type: -

Identifier Source: org_study_id