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

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

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.

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.

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.