P:II Above-Label Octreotide-LAR With Insufficiently Controlled Carcinoid Syndrome
Condition: Neuroendocrine Carcinoma
MeSH terms: Carcinoid Tumor; Carcinoma, Neuroendocrine; Malignant Carcinoid Syndrome; Serotonin Syndrome
Intervention: Octreotide LAR
Intervention description: Octreotide LAR as outlined in Treatment Arm.
Intervention MeSH terms: Octreotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: endocrine system; neuroendocrine tumors; neuroendocrine cancer; metastatic; neuroendocrine; gastrointestinal (GI); high-dose octreotide; flushing; diarrhea; quality of life in patients; disease-related symptoms

Summary:

      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.
    

Eligibility criteria:

        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.