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

Phase 2

Terminated

Conditions: Neuroendocrine Carcinoma

Interventions: Drug: Octreotide LAR

Registration Number: NCT01886287

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Brief 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Octreotide Long-acting Release (LAR)	Octreotide LAR	Octreotide LAR will be administered at a dose of 60 mg intramuscularly (IM) every 4 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Improved Frequency of Diarrhea	At 12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Rate of Progression Free Survival (PFS) at 6 Months	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.