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Study Summary
No. 2007-0778:.......Endocrine......Mouhammed A. Habra......Endocrine Neoplasia & Hormonal Disorders
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Study Summary Title
Study Summary
Number:
2007-0778
Study 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 Disease
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Physician New Patient Referral
Name:Mouhammed A. HabraPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Endocrine Neoplasia & Hormonal DisordersReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2841
Contact us about clinical trials
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General Information
Disease Group:EndocrineSupported By:Novartis
Phase of Study:Phase IIIReturn
Visit:
There are 18 visits spread out over a 14 month period. More visits will apply
if the patient elects to continue SOM230 following the 12 month study treatment
period.
Treatment
Agents:
SOM230Home Care:SOM230 will be self-administered by each study participant at home.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to learn if SOM230 (pasireotide)
can help to control Cushing's disease. Researchers will compare 2 dose levels
of the drug to find out which one may be more effective. The safety of this
drug will also be studied.
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Study Objectives / Outcomes
    Primary Objectives:
    To assess the efficacy in terms of response to pasireotide 600 mcg s.c. bid and 900 mcg s.c. bid independently in patients with Cushing's disease as measured by mean urinary free cortisol (UFC) </= 1.0 X the upper limit of normal (ULN) after 6 months of treatment.

    Secondary Objectives:
    · To assess reduction of mean UFC to ≤ 1.0 ULN at months 3 and 12.
· To assess time to first response
    · To assess the effect of pasireotide s.c. on plasma ACTH and serum cortisol as measured by the % change from baseline by treatment group.
· To assess median UFC response
    · To assess improvement in clinical signs: blood pressure, body mass index, waist circumference and weight reduction
    · To assess improvement in clinical symptoms of Cushing's disease: depression, facial rubor, buffalo hump, supraclavicular and dorsal fat pad, hirsutism, striae, muscle strength, bone density and body composition.
    · To assess the effect of pasireotide s.c. on tumor volume as evaluated with MRI scanning.
    · To assess censored-adjusted response
    · To assess pooled dose response
· To assess the response by dose group at intermediate visits.
    · To assess the effect of pasireotide s.c. on Quality of Life
    · To determine the pharmacokinetics of pasireotide after s.c. b.i.d. administration
    · To identify any patient related factors that may affect the pharmacokinetics or pharmacodynamics of pasireotide after s.c. b.i.d. dosing
    · To explore potential relationships between pharmacokinetics and pharmacodynamics s.c. b.i.d. dosing
    · To evaluate the safety and tolerability of pasireotide s.c. in patients with Cushing's disease

    Exploratory Objective
    · · To evaluate pasireotide 600 mcg s.c. bid and 900 mcg s.c. bid dose response longitudinally.
    · To evaluate midnight salivary cortisol level relation to serum cortisol and UFC levels.
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Study Status Information
Study Activation / Registration Date:07/18/2008
IRB Review and Approval Date:01/18/2008
Study Type:Phase Iii
Recruitment Status:Terminated
Projected Accrual:146
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Male or female patients aged 18 years or greater

2) Patients with diagnosis of ACTH-dependent Cushing's disease as evidenced by: (a) mean UFC from four 24-hour urinary collections at least 1.5 times the ULN collected within 2 weeks; (b) morning plasma ACTH within the normal or above normal range; (c) either MRI confirmation of a pituitary macroadenoma OR inferior petrosal sinus gradient >3 after CRH stimulation for tumors less than 1 cm* in size gradient >2 is required. If IPSS had not previously been performed, IPSS with CRH stimulation is required.

3) (continues # 2) OR histopathology confirming an ACTH staining adenoma for those patients who have had prior pituitary surgery. * if IPSS had previously been performed without CRH (e.g. eith 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.

4) Patients with de novo Cushing's disease can be included only if they are not considered candidates for pituitary surgery (i.e. poor surgery candidates, surgically unapproachable tumors, patients who refuse to have surgical treatment)

5) Confirmatory testing prior to inferior petrosal sinus sampling (low-dose dexamethasone suppression or dexamethasone-CRH testing) has to be performed for patients with 24-hour UFC levelst < / = 3 times the ULN AND a pituitary microadenomaon MRI in order to exclude possible pseudo-Cushing's syndrome.

6) Karnofsky performance status greater than or equal to 60 (i.e. requires occasional assistance, but is able to care for most of this personal needs).

7) For patients on medical treatment for Cushing's disease the following washout periods must be completed before baseline efficacy assessments are performed: (a) Inhibitors of steroidogenesis (ketoconazole, metyrapone, rosiglitazone): 1 week; (b) Dopamine agonists (bromocriptine, cabergoline): 4 weeks; (c) Octreotide LAR and Lanreotide autogel: 8 weeks; (d) Lanreotide SR: 4 weeks; (e) Octreotide immediate release formulation: 1 week

8) Patients with a known history of impaired fasting glucose or Diabetes Mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary

Exclusion Criteria:1) 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

2) Patients who have been treated with mitotane during the last 6 months.

3) 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

4) Patients with Cushing's syndrome due to ectopic ACTH secretion

5) Patients with hypercortisolism secondary to adrenal tumors or Nodular (primary) bilateral adrenal hyperplasia

6) Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e. Carney Complex, McCune-Albright syndrome, MEN-1)

7) Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)

8) Patients who are hypothyroid and not on adequate replacement therapy

9) Patients who have undergone major surgery within 1 month prior to starting the study

10) Patients with symptomatic cholelithiasis

11) Diabetic patients on antidiabetic medications whose fasting blood glucose is poorly controlled as evidenced by HbA1C >8%

12) Patients with abnormal coagulation (PT or PTT elevated by 30% above normal limits)

13) Patients receiving anticoagulants that affect PT or PTT

14) Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically symptomatic bradycardia, advanced heart block, history of acute myocardial infarction less than one year prior to study entry or clinically significant impairment in cardiovascular function

15) 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

16) 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

17) Patients with WBC <3 X 10^9/L; Hgb < LLN: PLT<100x10*9/L

18) 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

19) 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

20) 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

21) Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving pasireotide

22) Patients who have given a blood donation (of 400 ml or more) within 2 months before receiving pasireotide

23) Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing and patients who have been treated with pasireotide.

24) Known hypersensitivity to somatostatin analogues

25) Patients with active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix)

26) Patients with the presence of active or suspected acute or chronic uncontrolled infection

27) 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

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Links
Registration Number: NCT00434148
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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