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Cushing's DiseasePhase 2NCT02484755

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

A Phase 2 study testing Gefitinib in people with Cushing's Disease and Corticotrophin Adenoma, run by Huashan Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Cushing's Disease, Corticotrophin Adenoma
What is being tested?
Gefitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteChina
Study dates
Jun 2015to Sep 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients aged 18 years or greater
  • Patients with confirmed diagnosis of ACTH-dependent Cushing's disease as evidenced by
  • Mean urinary free cortisol of four 24-hour urine samples collected within 2 weeks, at least 1.5 times the upper limit of the laboratory normal range
  • Morning plasma ACTH within the normal or above normal range
  • Either MRI confirmation of pituitary macroadenoma (greater than or equal to 1 cm), or inferior petrosal sinus gradient >3 after CRH stimulation for those patients with a microadenoma (tumor less than 1 cm)*, or for patients who have had prior pituitary surgery, histopathology confirming an ACTH staining adenoma.
  • if IPSS had previously been performed without CRH (e.g.with DDAVP), then a central to peripheral pre-stimulation gradient > 2 is required. If IPSS had not previously been performed, IPSS with CRH stimulation is required.
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  • Patients with de novo Cushing's disease can be included only if they are not considered candidates for pituitary surgery (e.g. poor surgical candidates, surgically unapproachable tumors, patients who refuse to have surgical treatment)
  • Confirmatory testing prior to IPSS (low-dose dexamethasone suppression testing or dexamethasone-CRH testing) has to be performed for patients with UFC ≤ 3.0 X ULN and a pituitary microadenoma in order to exclude possible pseudo-Cushing's syndrome.
  • Karnofsky performance status ≥ 60 (i.e. requires occasional assistance, but is able to care for most of this personal needs)
  • For patients on medical treatment for Cushing's disease the following washout periods must be completed before baseline efficacy assessments are performed
  • Inhibitors of steroidogenesis (ketoconazole, metyrapone, rosiglitazone): 1 week
  • Dopamine agonists (bromocriptine, cabergoline): 4 weeks
  • Octreotide LAR and Lanreotide autogel: 8 weeks
  • Lanreotide SR: 4 weeks
  • Octreotide (immediate release formulation): 1 week
  • Patients with a known history of impaired fasting glucose or DM may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary

Who cannot join

  • Patients who have received pituitary irradiation within the last ten years prior to visit 1, as the onset time of the radiation effects cannot be determined
  • Patients who have treated with mitotane during the last 6 months prior to Visit 1
  • Patients with compression of the optic chiasm causing any visual field defect, in order to exclude patients with a tumor causing chiasma compression requiring surgery
  • Patients with Cushing's syndrome due to ectopic ACTH secretion
  • Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
  • Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e. Carney Complex, McCune-Albright syndrome, MEN-1)
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  • Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)
  • Patients who are hypothyroid and not on adequate replacement therapy
  • Patients who have undergone major surgery within 1 month prior to starting the study
  • Patients with symptomatic cholelithiasis
  • Diabetic patients on antidiabetic medications whose fasting blood glucose is poorly controlled as evidenced by HbA1C >8%
  • Patients with abnormal coagulation (PT or PTT elevated by 30% above normal limits)
  • Patients receiving anticoagulants that affect PT or PTT
  • Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute MI less than one year prior to study entry or clinically significant impairment in cardiovascular function
  • Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTc >480 ms, hypokalemia, family history of long QT syndrome, and concomitant medications known to prolong QT interval
  • Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with ALT/AST more than 2 X ULN, serum creatinine >2.0 X ULN, serum bilirubin >2.0 X ULN, serum albumin < 0.67 X LLN
  • Patients with WBC <3 X 109/L; Hgb < LLN; PLT <100 X 109/L
  • Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator or the sponsor's medical monitor
  • Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method for birth control. Female patients must use barrier contraception with condoms. If oral contraception is used, the patient must have been practicing this method for at least two months prior to enrollment and must agree to continue the oral contraceptive throughout the course of the study and for one month after the last dose of study drug. Male patients who are sexually active are required to use condoms during the study and for 1 month afterwards
  • History of immunocompromise, including a positive HIV test result (Elisa and Western blot). An HIV test will not be required, however, previous medical history will be reviewed
  • Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving pasireotide
  • Patients who have given a blood donation (of 400 ml or more) within 2 months before receiving gefitinib
  • Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing and patients who have previously been treated with gefitinib
  • Known hypersensitivity to gefitinib
  • Patients with active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix)
  • Patients with the presence of active or suspected acute or chronic uncontrolled infection
  • Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study

Trial locations and contacts

1 site in 1 country.

Ming Shen, MD contact

+86 13818795785

samshenming@yahoo.com

China1 site, 1 recruiting

  • Huashan Hospital

    Shanghai, Shanghai Municipality, 200040

    Ming Shen, MD, +86 13818795785, samshenming@yahoo.com

    Yao Zhao, MD

    Recruiting

Other trials in China

About this study

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.

Being tested
Gefitinib
Medical subject headings
Pituitary ACTH Hypersecretion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02484755
Study groupRoleWhat they receive
gefitinibExperimentalgifitinib 250 mg oral administration once daily for a total of 4 weeks.
Receives: Drug: Gefitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in levels of 24 hour urinary free cortisol after 4 weeks

    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%.

    Measured: Baseline, Week 4

Secondary outcomes (6)

  1. Number of participants with a normalized 24 hour urinary free cortisol after 4 weeks

    Measured: 4 weeks

  2. Change in levels of Late-Night Salivary Cortisol after 4 weeks

    Measured: Baseline, Week 4

  3. Change in levels of pituitary hormones （a composite of pituitary panel)

    Pituitary Panel (TSH,FT4, FT3, PRL, IGF-1, FSH, Testosterone Total, Free Testosterone, Estradial, SHBG)

    Measured: Baseline, Week 4

  4. Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    Measured: 4 weeks

  5. Changes in tumor size

    Measured: Baseline, Week 4

  6. Changes in clinical signs (the typical signs of Cushing's Disease such as facial rubor, hirsutism, striae, bruising and supraclavicular and dorsal fat pad)

    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.

    Measured: Baseline, Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jun 2015 (estimated)
  2. Study startJun 2015
  3. Primary completionSep 2015 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02484755
Sponsor's protocol ID
KY2015-167
Status last verified
Jun 2015
First submitted
21 Jun 2015
Last updated
30 Jun 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gefitinib in people with Cushing's Disease and Corticotrophin Adenoma, run by Huashan Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 30 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ming Shen, MD (+86 13818795785, samshenming@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in levels of 24 hour urinary free cortisol after 4 weeks (time frame: Baseline, Week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02484755.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2015.

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