P:II Above-Label Octreotide-LAR With Insufficiently Controlled Carcinoid Syndrome

Study Overview
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Brief Summary
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The primary purpose of the study is to investigate the effects of high-dose octreotide on flushing, diarrhea, and quality of life in patients whose disease-related symptoms are inadequately controlled by the maximum approved dose of octreotide LAR.

Detailed Description
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The study population will consist of patients with advanced (metastatic or unresectable) neuroendocrine tumors with suboptimally controlled carcinoid syndrome. While the majority of patients will have primary tumors of the ileocecum (midgut), any serotonin-producing neuroendocrine tumors will be eligible (including pancreatic, lung and unknown primary). All patients will be followed for adverse events and serious adverse events for 28 days following the last dose of above-label octreotide, or until resolution or stabilization of the event, whichever comes first.

Official Title
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Phase II Study of Above-Label Octreotide-LAR in Patients With Insufficiently Controlled Carcinoid Syndrome

Conditions
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Neuroendocrine Carcinoma

Intervention / Treatment
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* Drug: Octreotide LAR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic neuroendocrine tumors that are considered well or moderately differentiated (or low to intermediate grade). Patients with poorly differentiated neuroendocrine carcinomas or small cell carcinomas are excluded from the study. Elevated urine 5-hydroxyindoleacetic acid (5-HIAA) More than 2 bowel-movements per day OR more than 4 flushing episodes per week on average Patient currently on octreotide LAR 30mg every 3 or 4 weeks (for at least 3 cycles prior to screening) Age ≥ 18 years Minimum of four weeks since any major surgery, liver-directed therapy (embolization, etc.) or systemic cancer treatment other than octreotide LAR Eastern Cooperative Oncology Group (ECOG) performance status ≤2 Life expectancy > 12 weeks Reliable contraception should be maintained throughout the study and for 3 months after study drug discontinuation. Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information. Exclusion Criteria: Known hypersensitivity to somatostatin analogues Patients with poorly differentiated neuroendocrine cancers Patients with liver cirrhosis Patients receiving hemodialysis or peritoneal dialysis Patients with cachexia who, in the opinion of the investigator, may have difficulty tolerating intramuscular injection Patients with symptomatic cholelithiasis or biliary events within past five years (who have not undergone cholecystectomy) Patients with recent history (within 5 years) of pancreatitis Patients with uncontrolled diabetes (HgA1c >8.0 despite adequate therapy) Women of child-bearing potential, UNLESS they are using two birth control methods Women who are pregnant or lactating HIV positive patients History of sustained ventricular tachycardia, ventricular fibrillation, advanced heart block, idiopathic syncope thought to be related to ventricular arrhythmia, or congenital long QT syndrome Risk factors for Torsades de Pointes such as cardiac failure, clinically significant/symptomatic bradycardia Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study History of noncompliance to medical regimens or unwillingness to comply with the protocol Patients who were unable to tolerate or did not benefit from above-label dose octreotide (>30mg) in the past Concomitant use of other cancer treatments or carcinoid syndrome treatments (whether standard or experimental). Patients should discontinue any concomitant cancer medications more than two weeks prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Octreotide Long-acting Release (LAR)<br>Octreotide LAR will be administered at a dose of 60 mg intramuscularly (IM) every 4 weeks. | Drug: Octreotide LAR<br>* Octreotide LAR as outlined in Treatment Arm.<br>* Other names: Sandostatin LAR®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Improved Frequency of Diarrhea | The frequencies of flushing, diarrhea, and carcinoid syndrome control rating (scale 1-5) will be measured and compared at week 0 and week 12 . These measurements will be compared using two-sided non-parametric paired Wilcoxon signed-rank. | At 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Progression Free Survival (PFS) at 6 Months | Progression-free survival, defined as rate of patients alive and free of progression from the date of first study treatment to the end of trial at 6 months. Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. | At 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endocrine system, neuroendocrine tumors, neuroendocrine cancer, metastatic, neuroendocrine, gastrointestinal (GI), high-dose octreotide, flushing, diarrhea, quality of life in patients, disease-related symptoms