Clinical Trial: Targeted Therapy With Gefitinib in Patients With USP8-mutated Cushing's Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Targeted Therapy With Gefitinib in Patients With USP8-mutated Cushing's Disease

Brief Summary: The USP8 gene and its downstream target, epidermal growth factor receptor (EGFR), is a potential therapeutic target of Cushing disease. The EGFR inhibitor, Gefitinib, has been shown to reduce the production of ACTH both in vitro and in vivo, especially in USP8-mutated corticotrophin adenomas. The investigators hypothesize that Gefitinib will suppress pituitary corticotroph tumor ACTH production and normalize urinary free cortisol levels in patients with USP8-mutated Cushing's disease. Gefitinib is an FDA approved drug used to treat non-small cell lung cancer. However, in this study, the drug will be used to treat corticotrophin adenoma.

Detailed Summary:
Sponsor: Huashan Hospital

Current Primary Outcome: Change in levels of 24 hour urinary free cortisol after 4 weeks [ Time Frame: Baseline, Week 4 ]

Full response is defined as the reduction of 24 hour urinary free cortisol more than 50% or normalized. Partial response is defined as the reduction of 24 hour urinary free cortisol between 25%~ 50%. Poor response or resistance is defined as the reduction of 24 hour urinary free cortisol less than 25%.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of participants with a normalized 24 hour urinary free cortisol after 4 weeks [ Time Frame: 4 weeks ]
  • Change in levels of Late-Night Salivary Cortisol after 4 weeks [ Time Frame: Baseline, Week 4 ]
  • Change in levels of pituitary hormones （a composite of pituitary panel) [ Time Frame: Baseline, Week 4 ]
    Pituitary Panel (TSH,FT4, FT3, PRL, IGF-1, FSH, Testosterone Total, Free Testosterone, Estradial, SHBG)
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 4 weeks ]
  • Changes in tumor size [ Time Frame: Baseline, Week 4 ]
  • Changes in clinical signs (the typical signs of Cushing's Disease such as facial rubor, hirsutism, striae, bruising and supraclavicular and dorsal fat pad) [ Time Frame: Baseline, Week 4 ]

    The following symptoms will be evaluated using photographs taken at baseline and at the end of the study (Week 4):

    facial rubor, hirsutism, striae, bruising and supraclavicular and dorsal fat pad. The photographs will be assessed (scored) by the investigator as well as a second qualified physician at the site, who is blinded to the timepoint at which the photographs were taken.



Original Secondary Outcome: Same as current

Information By: Huashan Hospital

Dates:
Date Received: June 21, 2015
Date Started: June 2015
Date Completion:
Last Updated: June 29, 2015
Last Verified: June 2015