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

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01886287
• Collaborator: Novartis (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 10
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Carcinoma	Drug: Octreotide LAR	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Above-Label Octreotide-LAR in Patients With Insufficiently Controlled Carcinoid Syndrome
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Novartis

Investigators

• Principal Investigator: Jonathan Strosberg, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01886287
• Other Study ID Numbers: MCC-17410; CSMS995AUS64T
• First Posted: Jun 25, 2013
• Last Update Posted: Jan 12, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: endocrine system; neuroendocrine tumors; neuroendocrine cancer; metastatic; neuroendocrine; gastrointestinal (GI); high-dose octreotide; flushing; diarrhea; quality of life in patients; disease-related symptoms
• Additional relevant MeSH terms: Carcinoid Tumor; Carcinoma, Neuroendocrine; Malignant Carcinoid Syndrome; Serotonin Syndrome; Octreotide

Study Results

Participant Flow

Recruitment Details	This study was open to accrual at Moffitt Cancer Center 12/10/2013 through 10/10/2014.

Arm/Group Title	Octreotide Long-acting Release (LAR)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	2
COMPLETED	0
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Octreotide Long-acting Release (LAR)
Arm/Group Description	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.
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 50%
>=65 years	1 50%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Improved Frequency of Diarrhea
Description	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

Outcome Measure Data

Analysis Population Description

Participants on study at 12 weeks

Arm/Group Title	Octreotide Long-acting Release (LAR)
Arm/Group Description	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.
Measure Participants	1
Number [participants]	1 50%

2. Secondary Outcome

Title	Rate of Progression Free Survival (PFS) at 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

Evaluable participants on study at 6 months

Arm/Group Title	Octreotide Long-acting Release (LAR)
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Time Frame	3 months
Arm/Group Title	Octreotide Long-acting Release (LAR)
Arm/Group Description	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.
All Cause Mortality
	Octreotide Long-acting Release (LAR)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Octreotide Long-acting Release (LAR)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Octreotide Long-acting Release (LAR)
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Blood and lymphatic system disorders
Anemia	1/2 (50%)	1
Gastrointestinal disorders
Nausea	1/2 (50%)	1
Vomiting	1/2 (50%)	1
General disorders
Edema limbs	1/2 (50%)	1
Edema trunk	1/2 (50%)	1
Fatigue	1/2 (50%)	1
Injury, poisoning and procedural complications
Bruising	1/2 (50%)	1
Investigations
Blood bilirubin increased	1/2 (50%)	1
Weight loss	1/2 (50%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/2 (50%)	1
Hyperkalemia	1/2 (50%)	1
Hypokalemia	1/2 (50%)	1
Vascular disorders
Hypertension	1/2 (50%)	1

Limitations/Caveats

This study was closed early due to slow accrual. There were no evaluable participants at 6 months for the planned Progression Free Survival measure.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.