Metastatic carcinoid tumors whose disease-related symptoms are inadequately controlled by somatostatin analogues MedDRA version: 14.1 Level: LLT Classification code 10007271 Term: Carcinoid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female patients aged 18 years or greater. • Patients with histopathologically confirmed (from primary or metastatic lesion biopsy) metastatic carcinoid tumors of the digestive system with extent of disease determined by Computer Tomography (CT) scan or Magnetic Resonance Imaging (MRI). • Patients must have inadequate control of symptoms (i.e. diarrhea and/or flushing) while receiving treatment with a maximum approved dose of a currently available somatostatin analogue for at lease 3 months prior to study entry (as specified in Table 4-1). Inadequate control is defined by groups below: • Diarrhea and Flushing group (D+F): patients with a daily mean of > 4 bowel movements and a total of > 5 flushing episodes over a two-week period (14 days) while receiving treatment with a maximum approved dose of currently available somatostatin analogue for at least a 3 month period prior to study entry (as specified in Table 4-1). • Predominantly Diarrhea group (D): patients with a daily mean of > 4 bowel movements and a total number 14 flushing episodes and a daily mean of 60 • Patients must observe the following intervals between the last injection of their previous treatment and the first injection of study drug: • Octreotide LAR = 28 days (4 weeks) • Octreotide s.c. = 8 hours • Lanreotide Autogel = 28 days (4 weeks) • Lanreotide SR = 14 days (2 weeks) • 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 (see Section 6.6.2.1) • Female patients of child bearing potential must have a negative pregnancy test at baseline. • Patients for whom written informed consent to participate in the study has been obtained. • Baseline lab values for adequate organ function: • Absolute neutrophil count > 1.5 x 10 9/L • Hemoglobin >9 g/dL • Platelets > 100 x 10 9/L • Hepatic: Serum bilirubin = 1.5 X upper limit of normal (ULN), Aspartate aminotransferase and alanine aminotransferase, =3 × ULN without liver metastases, =5 × ULN if documented liver metastases. • Renal: Serum creatinine =2 mg/dL, calculated creatinine clearance =30 mL/min • Potassium: Serum potassium = 3.5 mEq/L 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients who have received a somatostatin analogue higher than the maximum approved dose within 3 months of Visit 1. (This exclusion criteria is not applicable to patients who are receiving short acting formulation.) • Patients receiving radiolabeled somatostatin analogue therapy within the 3 months or any cytotoxic chemotherapy or interferon therapy within the 4 weeks prior to recording baseline symptoms • Patients who have undergone major surgery/surgical therapy for any cause within 1 month or surgical therapy of loco-regional metastases within the last 3 months before recording baseline symptoms • Patients with hepatic artery embolization, chemoembolization or radioembolization (ytrium 90 microsphere) treatmetn within the last 6 months (1 month if there are other sites of measurable disease), or patients who have undergone cryoablation or radiofrequency ablation of hepatic metastasis within the last 2 months before recording baseline symptoms • Patients who have received radiotherapy for any reason within the last 4 weeks must have recovered from any side effects of radiotherapy before recording baseline symptoms • Patients who are unwilling to follow dietary restrictions (see Section 7.4.2.7) within 3 days of urinary 5-HIAA sample collection or require medications that would interfere with urinary 5-HIAA measurement (e.g. Reserpine, mephenesin carbamate, Lugol’s solution) • Patients with known malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means • Patients who are not biochemically euthyroid • Diabetic patients on antidiabetic medications whose fasting blood glucose is poorly controlled as indicated by HbA1C > 8% • Patients with symptomatic cholelithiasis • Any of the following cardiac abnormalities: • QTcF at screening > 470 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 couuld prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinsons disease), HIV cirrhosis, uncontrolled hypothyroidism or cardiac failure. • Concomitant medication (s) known to increase the QT interval. • Patients with additional 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 or with a history of immunocompromise, including a positive HIV test result (ELISA andWestern blot). A HIV test will not be required; however, previous medical history will bereviewed • Patients with abnormal coagulation (PT or APTT elevated by 30% above normal limits) • Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator or the Sponsors Study physician. • Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. Female patients must use barrier contraception with condoms. If oral contraception is used in addition to condoms, the patient must have been practicing this method for at least two months prior to enrollment and must agree to c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the long term efficacy of pasireotide LAR vs. octreotide LAR at 6 months in controlling diarrhea and/or flushing in patients with metastatic carcinoid tumors whose disease-related symptoms are inadequately controlled by the maximum approved doses of somatostatin analogues.;Secondary Objective: Main Secondary Objective: • Assess the effect of pasireotide LAR vs octreotide LAR on objective tumor response rate (CR or PR) at months 6 based on RECIST criteria. •Assess the effect of pasireotide LAR vs octreotide LAR on disease control rate (CR, PR or SD) at month 6 based on RECIST criteria. • Assess the proportion of patients who achieved at least 30% reduction in frequency of bowel movements at month 6. • Assess the effect of pasireotide LAR vs octreotide LAR on: - improvement in the individual components of the primary endpoints (i.e. percent change in daily bowel movement and/or total number of flushing) - time to symtpom response - duration of symtom response - time to symptomprogression - Quality of Life • Assess the overall safety and tolerabiliyt of pasireotide LAR vs octreotide LAR • Assess the overall safety and tolerability of pasireotide LAR vs. octreotide LAR;Primary end point(s): The primary endpoint is based on the mean number of bowel movements and/or total number of flushing episodes at month 6. | — |
Countries
Austria, Belgium, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed