Neuroendocrine Carcinoma
Conditions
Keywords
endocrine system, neuroendocrine tumors, neuroendocrine cancer, metastatic, neuroendocrine, gastrointestinal (GI), high-dose octreotide, flushing, diarrhea, quality of life in patients, disease-related symptoms
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.
Interventions
DRUGOctreotide LAR
Octreotide LAR as outlined in Treatment Arm.
Sponsors
Novartis
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
This study was open to accrual at Moffitt Cancer Center 12/10/2013 through 10/10/2014.
Participants by arm
| Arm | Count |
|---|---|
| Octreotide Long-acting Release (LAR) Octreotide LAR will be administered at a dose of 60 mg intramuscularly (IM) every 4 weeks.
Octreotide LAR: Octreotide LAR as outlined in Treatment Arm. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Clinical progression due to disease | 1 |
| Overall Study | Radiographic disease progression | 1 |
Baseline characteristics
| Characteristic | Octreotide Long-acting Release (LAR) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 63 years |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
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.
Time frame: At 12 weeks
Population: Participants on study at 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Octreotide Long-acting Release (LAR) | Number of Participants With Improved Frequency of Diarrhea | 1 participants |
Secondary
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.
Time frame: At 6 months
Population: Evaluable participants on study at 6 months