To assess the efficacy and safety of two Pasireotide LAR regimens in CD patients.
ID
Source
Brief title
Condition
- Hypothalamus and pituitary gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
proportion of patients with mUFC * 1 x ULN at month 7 regardless of up
titration at Month 4
Secondary outcome
proportion of patients with mUFC * 1 x ULN at month 7 for patients who did not
up titrate dose at Month 4
Background summary
For patients with Cushing's disease (CD), surgical removal of the pituitary
adenoma is the first line therapy. Irradiation of the pituitary is another
treatment option but it may take many years to be effective and it is curative
in only 15 to 45% of the cases.
When surgery and/or irradiation fail, or for those patients for whom such
therapies are not an option, the remaining alternatives are pharmacological
treatment or bilateral adrenalectomy. No drugs are currently approved for the
treatment of Cushing*s disease and the ones which physicians have available for
use are fraught with suboptimal results and significant side effects ( and the
majority are limited to inhibit steroidogenesis at the adrenals, not targeting
the pituitary adenoma. Bilateral adrenalectomy is a definite cure of Cushing*s
disease but results in irreversible primary adrenal insufficiency and patients
need lifelong replacement therapy with glucocorticoids and mineralocotricoids
and have a higher likelihood to develop Nelson*s syndrome.
Therefore, a safe and effective targeted medical therapy is highly desirable in
this patient population. There is an unmet medical need for the treatment of CD
as medical treatment options are limited. Recent trials have showed that the
subcutaneously administered form of pasireotide is efficacious in CD patients.
This study aims to find out if and which dose of the Long Acting Release form
is efficacious in CD.
Study objective
To assess the efficacy and safety of two Pasireotide LAR regimens in CD
patients.
Study design
This is a global, multi-center, randomized, double-blind, phase III study.
After a screening period, patients who meet all eligibility criteria will be
randomized in a 1:1 ratio to receive one of two pasireotide LAR regimens
(starting dose of either 10 mg or 30 mg i.m. administered once every 28 days
for 4 months, followed by dose up-titration or continuation of the starting
dose). Randomization will be stratified based on baseline mean Urinary Free
Cortisol (mUFC) values to ensure a balanced distribution of baseline mUFC in
the 2 treatment arms. Patients will be evaluated monthly for 12 months where
mUFC will be determined over 14 days. The primary efficacy variable will be
assessed at Month 7.
After Month 7, all patients will be assessed for mUFC response by the
investigator and may be allowed to continue in the study up to Month 12.
Investigators and pertinent study staff only will be unblinded after the
patient has completed the Month 7 visit. At the end of the 12 month treatment
period, patients will be evaluated for mUFC response and will either
discontinue or continue on to the extension study.
Total duration of the core study will be 14 months including 1 month of
screening, 12 months of treatment, and a follow-up visit. The extension study
will be 12 months of treatment.
Intervention
Treatment with pasireotide LAR.
Study burden and risks
Toxicity of pasireotide LAR therapy.
Radiation exposure, DXA scan;
Frequent visits and blood sampling
An overview of all procedures during the visits are given in Appendix C of the
patient information
The side effects can be found in Appendix D of the patient information.
It is not certain that participation in the research directly benefit, the data
can be useful for future patients.
The burden on the patients is as expected for a phase III trial.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
2. Adult patients with confirmed diagnosis of ACTH-dependant Cushing*s disease
3. 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)
4. Confirmation that pseudo-Cushing*s is excluded for patients with mUFC * 3 x ULN
6. Karnofsky performance status * 60 (i.e. requires occasional assistance, but is able to care for most of their personal needs)
7. For patients on medical treatment for Cushing*s disease the washout periods must be completed before screening assessments are performed
8. 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 study and adjusted as necessary.
Exclusion criteria
1. Patients who are considered candidates for surgical treatment at the time of study entry
2. Patients who have received pituitary irradiation within the last ten years prior to visit 1
3. Patients who have had any previous pasireotide treatment
4. Patients who have been treated with mitotane during the last 6 months prior to Visit 1
5. Patients with compression of the optic chiasm causing any visual field defect that requires surgical intervention
6. Diabetic patients with poor glycemic control as evidenced by HbA1c >8%
7. Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF > 470 ms, hypokalemia, hypomagnesemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval
8. History of HIV infection, including a positive HIV test result (Elisa and Western blot). An HIV test will not be required, however, previous medical history will be reviewed
9. Patients with Cushing*s syndrome due to ectopic ACTH secretion
10. Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
11. Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e. Carney Complex, McCune-Albright syndrome, MEN-1)
12. Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)
13. Patients who are hypothyroid and have clinical symptoms of hypothyroidism despite adequate replacement therapy
14. Patients who have undergone major surgery within 1 month prior to starting the study
15. Patients with symptomatic cholelithiasis
16. Patients with abnormal coagulation (PT or PTT elevated by 30% above normal limits)
17. Patients receiving anticoagulants that affect PT or PTT
18. 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
19. Patients with history of liver disease such as cirrhosis, chronic active hepatitis B and C, or patients with ALT/AST more than 2 X ULN, serum bilirubin >1.5 X ULN
20. Patients with serum creatinine >2.0 X ULN,
21. Patients with WBC >3 X 109/L; Hgb 90% > LLN; PLT >100 X 109/L
31. Presence of Hepatitis B surface antigen (HbsAg)
32. Presence of Hepatitis C antibody (anti-HCV)
33. Known gallbladder or bile duct disease, acute or chronic pancreatitis
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-011128-70-NL |
| ClinicalTrials.gov | NCT01374906 |
| CCMO | NL37725.078.11 |