Laurence Katznelson
A randomized, double-blind study to assess the safety and efficacy of different dose levels of Pasireotide (SOM230) s.c. over a 6 month treatment period in patients with de novo, persistent or recurrent Cushing's disease
Contact Information
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Brief
Pasireotide is a novel cyclohexapeptide, somatostatin analogue developed as a follow-up to octreotide with a superior endocrine profile study.This study therefore is designed to assess the efficacy and safety of pasireotide in patients with both de novo and persistent or recurrent Cushing?s disease. After a 30 day screening period, patients who fulfill the entrance criteria wbe randomized in a double-blinded manner to receive pasireotide s.c. at a dose of either 600 or 900 ?g s.c. b.i.d. for three months via an Interactive Voice Response System (IVRS). After the first three months of treatment, patients will remain blinded and continue to receive the same dose for the next 3 months. The primary analysis will be performed after six months of treatment. There will be a 6-month open-label period thereafter when patients will continue with the same pasireotide dose.After 12 months of treatment, patients have the option to continue study treatment (extension Phase).
Recruiting Status:
RecruitingStanford Recruiting Status:
RecruitingCondition(s):
Intervention(s):
- Drug: Pasireotide subcutaneous (s.c.)
Phase:
Phase 3Eligibility
Ages Eligible for Study:
Any Age to Any AgeGenders Eligible for Study:
Male and FemaleHealth of Volunteers:
People with the conditions listed in this trial can participate as controls.Key Inclusion Criteria:
Male or female patients aged 18 years or greater
Patients with confirmed diagnosis of ACTH-dependent Cushing??s disease
as evidenced by
1. mean UFC from four 24-hour urinary collections at least 1.5 times thupper limit of the laboratory normal range collected within 2 weeks; 2. morning plasma ACTH within the normal or above normal range;3. 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.
# 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
Key Exclusion Criteria:
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)
# 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 knownto prolong QT interval
# Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistenthepatitis, 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 pasireotide
# 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 pasireotide
# Known hypersensitivity to somatostatin analogues
# 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
Additional Study Details
Official Title:
A randomized, double-blind study to assess the safety and efficacy of different dose levels of Pasireotide (SOM230) s.c. over a 6 month treatment period in patients with de novo, persistent or recurrent Cushing's diseaseAnticipated start date:
6/6/2007Lead Sponsor:
Novartis PharmaceuticalsInvestigator(s):
Study Type:
InterventionalPurpose:
TreatmentAllocation:
RandomizedMasking:
Double BlindControl:
noneAssignment:
ParallelEndpoints:
Safety/EfficacyPrimary Outcomes:
- Urinary Free Cortisol
- Plasma ACTH
- Serum cortisol
Secondary Outcomes:
- Clinical Signs and Symptoms of Cushing's Disease
- Quality of life
- Tumor size
- Safety Assessments and Laboratory tests
Total Number to be Enrolled:
150Total Number to be Enrolled at Stanford:
3More Information
Secondary ID(s):
- e-protocol 7665
Locations & Contacts
Stanford Locations & Contacts:
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Non-Stanford Locations:
The Stanford website does not have any locations outside of Stanford listed for this trial. You may want to check clinicaltrials.gov for posible additional locations.
This listing was last updated:
8/7/2008PLEASE NOTE:
Study Coordinators and Research Nurses cannot give medical advice over the phone. Telephone numbers are provided for obtaining additional information on specific clinical research trials only. If you have specific questions which require clinical expertise, please call your primary care physician. If you do not have a primary care physician please feel free to call the SHC Physician Referral Service at (800) 756-9000 or send an email.
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