Cabergoline Combined Hydroxychloroquine/Chloroquine to Treat Resistant Prolactinomas
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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 Design
Arms and Interventions
| 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:
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Outcome Measures
Primary Outcome Measures
- Change from baseline on prolactin(PRL) level [Up to 6 months]
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） [Up to 6 months]
Record the tumor volume from enhanced pituitary MRI on every 3 month follow-up visits
- Change from baseline of visual acuity [Up to 6 months]
Record the Visual acuity on every 3 month follow-up visit
- Change from baseline on 5 point visual field scale [Up to 6 months]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged between 18 and 70 years old, either sex;
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Karnofsky performance status ≥ 70;
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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%;
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The patient has signed the informed consent.
Exclusion Criteria:
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Patients concomitantly taking the psychotropic drugs or other drugs causing elevated PRL ;
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Patients with parkinson disease and is taking dopaminergic agents;
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Patients with prolactinoma who received Gamma knife treatment;
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Patients who use any dopamine receptor agonists other than cabergoline;
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pregnant or lactating women, or women preparing pregnant;
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Patients with poor compliance, who cannot implement the program strictly.
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History of allergic reactions attributed to compounds of similar chemical or biologic composition to HCQ.
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency, as HCQ may cause hemolytic anemia in patients with G6PD deficiency.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Tiantan Hospital | Beijing | Beijing | China | |
| 2 | Huashan Hospital | Shanghai | Shanghai | China | 200025 |
| 3 | Ruijin Hosipital | Shanghai | Shanghai | China | 200025 |
| 4 | Chinese PLA General Hospital | Beijing | China | ||
| 5 | Peking Union Medical College Hospital | Beijing | China | ||
| 6 | Xinqiao Hospital of Chongqing | Chongqing | China | ||
| 7 | First Affiliated Hospital of Fujian Medical | Fujian | China | ||
| 8 | First Hospital of China Medical University | Shenyang | China | ||
| 9 | First Affiliated Hospital of Wenzhou Medical Univeristy | Wenzhou | China |
Sponsors and Collaborators
- Zhebao Wu
- 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
Investigators
- Study Chair: Zhebao Wu, Medical, Ruijin Hospital
Study Documents (Full-Text)
None provided.More Information
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.
- HCCT-2018