The purpose of this study, is to evaluate the efficacy and safety of pasireotide alone or in combination with cabergoline in patients with Cushing*s disease as measured by the proportion of patients achieving normal UFC at the end of the study…
ID
Source
Brief title
Condition
- Hypothalamus and pituitary gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients who attain mUFC <1.0xULN at week 35 with pasireotide
alone or in combination with cabergoline
Secondary outcome
1. Actual and percentage change in mUFC from baseline to study end at each
scheduled visit when UFC is measured
2. Proportion of patients that attain mUFC * 1.0xULN as assessed at each
scheduled visit when UFC is measured
3. Proportion of patients who attain mUFC * 1.0xULN or have at least 50%
reduction from baseline in mUFC as assessed at each scheduled visit when UFC is
measured
4. Duration of controlled or partially controlled response
5. Change from baseline in plasma ACTH and serum cortisol over time
6. Actual and percentage change from baseline in clinical symptoms over time:
blood pressure, body mass index, waist circumference, fasting serum lipid
profile, and weight
7. Shift from baseline in clinical signs over time: facial rubor, fat pads,
hirsutism, striae (via photographs) and muscle strength
8. Change from baseline in standardized scores, as measured by the Cushing*s
QOL and SF-12v2 over time
9. Ctrough and Cmax at baseline, week 8 and week 17
10. Toxicity will be assessed using the National Cancer Institute-Common
Toxicology Criteria Adverse Events version 4.0 (NCI-CTCAE v.4) and for
laboratory assessments that include biochemistry, hematology, urinalysis;
special safety assessments that include the regular monitoring and recording of
blood glucose, insulin, HbA1c, GH and IGF-1, thyroid and liver function tests,
gallbladder examinations and ECGs. Concomitant medications/Significant nondrug
therapies will be assessed from study enrollment until the safety follow-up
visit.
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.
Pasireotide is currently approved for the treatment of Cushing*s disease, but
does not optimally benefit all CD patients.
The non-approved treatments 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.
There is an unmet medical need for the treatment of CD for patients where
pasireotide alone does not provide optimally benefit.
Study objective
The purpose of this study, is to evaluate the efficacy and safety of
pasireotide alone or in combination with cabergoline in patients with Cushing*s
disease as measured by the proportion of patients achieving normal UFC at the
end of the study period.
Study design
This is an open-label, two group, multi-center international non-comparative
study.
Intervention
Treatment with pasireotide alone or in combination with cabergoline.
Study burden and risks
Toxicity of pasireotide and cabergoline therapy.
Frequent visits and blood sampling.
An overview of all procedures during the visits are given in the patient
information. The side effects can be found in the patient information as well.
It is not certain that participation in the trial will provide direct benefit,
the data can be usefull for future patients.
The burden on the patients is as expected for a phase II trial.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for Group 1:
1. Adult patients with confirmed diagnosis of ACTH-dependent Cushing*s disease
2. Patients with de novo Cushing*s disease can be included only if they are not considered candidates for pituitary surgery
3. Male or female patients aged 18 years or greater
4. Karnofsky performance status * 60 (i.e. requires occasional assistance, but is able to care for most of their personal
needs)
5.Patients on medical treatment for Cushing*s disease the following washout periods must be completed before
screening assessments are performed
6.Patients have been on pasireotide in the past but discontinued
because of lack of efficacy are also allowed to enter Group 1. Patients treated with pasireotide subcutaneously must have been discontinued from the treatment for at least 4 weeks before
screening. Patients treated with pasireotide LAR must have been
discontinued from the treatment for at least 12 weeks before screening.
7. Patients who meet the any one of the following critieria:
* They are naive to pasireotide
* They have recieved pasireatide in the past and have been discontinued bcause of lack of efficacy (2 weeks for pasireotide subcutaneously and 12 weeks of washout prior to screening for patients treated with pasireotide LAR)
8.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, if they are using
highly effective methods of contraception during dosing and for 30 days after stopping study medication.
Exclusion criteria
1. Patients with compression of the optic chiasm causing any visual field defect that requires surgical intervention
2. Diabetic patients with poor glycemic control as evidenced by HbA1c>8%
3. Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF>450 ms in males, and >460 ms in females, hypokalemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval.
4. Patients with clinically significant valvular disease.
5. Patients with Cushing*s syndrome due to ectopic ACTH secretion
6. Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
7. 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
8. Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with ALT/AST > 2 X ULN, serum bilirubin > 2.0 X ULN
9. Patients with serum creatinine >2.0 X ULN
10. Patients with WBC <3 X 10e9/L; Hb 90% < LLN; PLT <100 X 10e9/L
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 who are hypothyroid and not on adequate replacement therapy
13. Patients with symptomatic cholelithiasis
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 | EUCTR2013-002170-49-NL |
| ClinicalTrials.gov | NCT01915303 |
| CCMO | NL49601.078.14 |