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Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas

Primary Purpose

Resistance, Disease, Prolactinoma

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
HCQ/CQ and CAB combined treatment
Sponsored by
Zhebao Wu
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Resistance, Disease focused on measuring cabergoline, prolactinomas, resistant, hydroxychloroquine, chloroquine

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HCQ/CQ and CAB combined treatment

Arm Description

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

Outcomes

Primary Outcome Measures

Change from baseline on prolactin(PRL) level
Record the result of prolactin on every 3 month follow-up visit

Secondary Outcome Measures

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
Change from baseline of visual acuity
Record the Visual acuity on every 3 month follow-up visit
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

Full Information

First Posted
January 8, 2018
Last Updated
October 14, 2018
Sponsor
Zhebao Wu
Collaborators
Xinqiao Hospital of Chongqing, First Hospital of China Medical University, Beijing Tiantan Hospital, First Affiliated Hospital of Wenzhou Medical University, First Affiliated Hospital of Fujian Medical University, Peking Union Medical College Hospital, Huashan Hospital, Chinese PLA General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03400865
Brief Title
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

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Unknown status
Study Start Date
October 25, 2018 (Anticipated)
Primary Completion Date
December 30, 2020 (Anticipated)
Study Completion Date
December 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Zhebao Wu
Collaborators
Xinqiao Hospital of Chongqing, First Hospital of China Medical University, Beijing Tiantan Hospital, First Affiliated Hospital of Wenzhou Medical University, First Affiliated Hospital of Fujian Medical University, Peking Union Medical College Hospital, Huashan Hospital, Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Resistance, Disease, Prolactinoma
Keywords
cabergoline, prolactinomas, resistant, hydroxychloroquine, chloroquine

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HCQ/CQ and CAB combined treatment
Arm Type
Experimental
Arm Description
Subjects are treated with hydroxychloroquine sulfate tablets 5mg/kg Bid and cabergoline tablets 2mg/week for 3 months.
Intervention Type
Drug
Intervention Name(s)
HCQ/CQ and CAB combined treatment
Other Intervention Name(s)
HCCT
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from baseline on prolactin(PRL) level
Description
Record the result of prolactin on every 3 month follow-up visit
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Change from baseline on tumor volume measured by enhanced pituitary Magnetic Resonance Imaging（MRI）
Description
Record the tumor volume from enhanced pituitary MRI on every 3 month follow-up visits
Time Frame
Up to 6 months
Title
Change from baseline of visual acuity
Description
Record the Visual acuity on every 3 month follow-up visit
Time Frame
Up to 6 months
Title
Change from baseline on 5 point visual field scale
Description
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
Time Frame
Up to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged between 18 and 70 years old, either sex; Karnofsky performance status ≥ 70; 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%; The patient has signed the informed consent. Exclusion Criteria: Patients concomitantly taking the psychotropic drugs or other drugs causing elevated PRL ; Patients with parkinson disease and is taking dopaminergic agents; Patients with prolactinoma who received Gamma knife treatment; Patients who use any dopamine receptor agonists other than cabergoline; pregnant or lactating women, or women preparing pregnant; Patients with poor compliance, who cannot implement the program strictly. History of allergic reactions attributed to compounds of similar chemical or biologic composition to HCQ. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, as HCQ may cause hemolytic anemia in patients with G6PD deficiency.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shaojian Lin, MD
Phone
0086-15801782758
Email
shaojianlin88@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Zhebao Wu, Medical PhD
Phone
0086-021-64370045
Email
zhebaowu@aliyun.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhebao Wu, Medical
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Beijing Tiantan Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Huashan Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Ruijin Hosipital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Chinese PLA General Hospital
City
Beijing
Country
China
Facility Name
Peking Union Medical College Hospital
City
Beijing
Country
China
Facility Name
Xinqiao Hospital of Chongqing
City
Chongqing
Country
China
Facility Name
First Affiliated Hospital of Fujian Medical
City
Fujian
Country
China
Facility Name
First Hospital of China Medical University
City
Shenyang
Country
China
Facility Name
First Affiliated Hospital of Wenzhou Medical Univeristy
City
Wenzhou
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing 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.
Citations:
PubMed Identifier
28613975
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.
Results Reference
background
PubMed Identifier
26513171
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.
Results Reference
background
PubMed Identifier
28973192
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.
Results Reference
result

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Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas

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