Patients with neuroendocrine tumors and carcinoid diarrhea MedDRA version: 15.1 Level: LLT Classification code 10062476 Term: Neuroendocrine tumor System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Signifor 0.6 mg s.c.
Pharmaceutical Form: Injection
INN or Proposed INN: Pasireotide
CAS Number: 396091-73-9
Other descriptive name: PASIREOTIDE
Concentration unit: mg/ml milligram(s)/mill
Sponsors
Klaus Krogh
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In substudy 1 and 2 all inclusion criteria listed below have to be fulfilled. In substudy 3 and 4 inclusion criteria 1-7 have to be fulfilled. 1. Male or female patients ? 18 years of age 2. NET confirmed by histology 3. Diarrhea, (at least 3 bowel movements per day) as part of carcinoid syndrome 4. Treatment naïve or without treatment with long-acting SA for at least eight weeks or short acting SA for at least 14 days 5. WHO/ ECOG Performance Status of 0-2. 6. Life expectancy ?12 weeks 7. Written informed consent obtained prior to any screening procedures 8. Patients with a known history of impaired fasting blood glucose (glucose >100 and 5.5mmol/l and 30 ml/min/m2 • Serum amylase = 1.5 x ULN • Alkaline phosphatase = 2.5 x ULN 10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: In substudy 1 and 2 all exclusion criteria listed below have to be fulfilled. In substudy 3 and 4 exclusion criteria 1-5 have to be fulfilled. 1. Patients with known malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means. 2. Patients who have undergone major surgery/surgical therapy for any cause within 1 month. Patients should have recovered from the treatment and have good clinical condition before entering the study. 3. Patients who have any current or prior medical condition that may interfere with the conduct of the study or the study or the evaluation of its results. 4. Use of an investigational drug within 1 month prior to dosing 5. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study 6. Female patients who are pregnant or lactating, or are of childbearing potential (defined as all women physiologically capable of becoming pregnant) and not practicing an effective method of contraception/birth control. Sexually active males must use a condom during intercourse while taking the drug and for 2 months after the last dose of study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Effective contraception methods include: • Use of oral, injected or implanted hormonal methods of contraception or • Placement of an intrauterine device (IUD) or intrauterine system (IUS) • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository • Total abstinence or patient sterilization (male or female) 7. Patients with a known hypersensitivity to SA or any component of the pasireotide s.c. formulation. 8. Patients with abnormal coagulation (PT or aPTT elevated by 30% above normal limits). 9. Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion. 10. Patients with symptomatic cholelithiasis. 11. Patients who are not biochemically euthyroid. Patients with known history of hypothyroidism are eligible if they are on adequate and stable replacement thyroid hormone therapy for at least 3 months. 12. QT-related exclusion criteria: • QTcF at screening > 450 msec • History of syncope or family history of idiopathic sudden death • Sustained or clinically significant cardiac arrhythmias • Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block • Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure • Family history of long QT syndrome • Concomitant medications known to prolong the QT interval. • Potassium 8% despite adequate therapy, • Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunodeficiency, includi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare gastrointestinal transit times and motility patterns in NET patients, with diarrhea (3 or more bowel movements/day) when treated with either a) pasireotide 600 µg s.c. * 2/day or b) placebo. And To compare rectal wall properties and the postprandial response in NET patients, with diarrhea (3 or more bowel movements/day) when treated with either a) pasireotide 600 µg s.c. * 2/day or b) placebo. And To describe gastrointestinal transit times and motility patterns in NET patients, with diarrhea (3 or more bowel movements/day) and compare that to healthy subjects. And To describe rectal wall properties and the postprandial response in NET patients, with diarrhea (3 or more bowel movements/day) and compare that to healthy subjects. ;Secondary Objective: Not applicable;Primary end point(s): The difference in effect of pasireotide and placebo on gastrointestinal transit time and rectal wall stiffness in sub-study 1 and 2. The difference in gastrointestinal transit time and rectal wall stiffness between NET patients with carcinoid diarrhea and healthy subjects.;Timepoint(s) of evaluation of this end point: After 15 patients have gone through sub-study 1 and 2 or 3 and 4, however there will be a interim analysis after 10 patients have been through sub-study 1 and 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Sub-study 1: The difference in effect of pasireotide and placebo on: Small intestinal transit time Velocity through the small intestine Gastric emptying Orocecal transit time Colorectal transit time Number of bowel movements/day Number of flushing episodes/day Chromogranin A and serotonin levels Urinary 5HIAA excretion Sub-study 2: The difference in effect of pasireotide and placebo on: Postprandial changes in rectal cross sectional area Rectal compliance Ractal fasting tone Rectal sensibility to distension Rectal sensibility to temperature Sub-study 3: The difference between NET patients with diarrhea and healhty subjects on: Small intestinal transit time Velocity through the small intestine Gastric emptying Orocecal transit time Colorectal transit time Sub-study 4: The difference between NET patients with diarrhea and healhty subjects on Postprandial changes in rectal cross sectional area Rectal compliance Ractal fasting tone Rectal sensibility to distension Rectal sensibility to temperature ;Timepoint(s) of evaluation of this end point: After 15 patients have gone through the studies, however there will be a interim analysis after 10 patients have been through sub-study 1 and 2. | — |
Countries
Denmark
Contacts
Public ContactTine Gregersen
Tine Gregersen
Outcome results
None listed