Objective evaluation of the effects of pasireotide on gastrointestinal and colorectal transit times, rectal wall properties, and postprandial response in patients with carcinoid diarrhea

• Conditions: Patients with neuroendocrine tumors and carcinoid diarrhea; MedDRA version: 15.1Level: LLTClassification code 10062476Term: Neuroendocrine tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-003939-27-DK
• Lead Sponsor: Klaus Krogh

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-02-12
• Last Update Posted: 28 December 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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 <126 (>5.5mmol/l and <7 mmol/l)) may be included at the discretion of the PI. These patients will be monitored closely throughout the trial and anti-hyperglycemic treatment adjusted as necessary. Patients that are deemed non eligible due to elevated glucose can be re-screened after adequate medical treatment if not started in other SA treatment
9.Adequate end organ function as defined by:
•Adequate bone marrow function:
• WBC = 2.5 x 109/L
• Absolute Neutrophil Count (ANC) = 1.5 x 109/L
• Platelets = 100 x 109/L
• Hb = 9 g/dL (=5.6 mmol/l)
•No evidence of significant liver disease:
• Serum bilirubin =1.5 x ULN
• INR < 1.3
• ALT and AST = 3 x ULN
•Serum creatinine = 2.0 mg/dl and estimated glomerular filtration rate (eGFR) > 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

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 < or = 3.5 mmol/L

13.Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
•Uncontrolled diabetes as defined by HbA1c > 8% despite adequate therapy,
•Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunodeficiency, includi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified