High Dose Somatostatin Analogues in Neuroendocrine Tumors

Pancreatic Neoplasms Clinical Trial

— HIDONET  

Official title:

Efficacy and Safety of High Dose Regimen of Octreotide LAR in Patients With Neuroendocrine Tumors in Progressive Disease: A Phase II, Open, Multicentric Prospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00990535
• Other study ID #: NeuroendoUnit-6
• Status: Completed
• Phase: Phase 2
• First received: October 5, 2009
• Last updated: October 6, 2009
• Start date: January 2006
• Est. completion date: December 2008

Study information

• Verified date: October 2009
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of HealthItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

Octreotide (OCT) is a somatostatin analogue (SSA) available in a long-acting formulation, conventionally administered every 28 days at the maximum dose of 30 mg. Together with lanreotide, it is considered the therapy of choice in the control of endocrine syndromes associated with neuroendocrine tumors (NET)s. A complete or partial clinical response to SSA therapy is generally achieved in at least 50% of the patients with neuroendocrine syndrome. Many studies reported a clinical response in 70-90% of functioning NETs. In about 36-50% of the patients with progressive advanced well differentiated NET (WDNET), a stabilization of disease occurs after treatment with subcutaneous OCT. By developing long-acting slow-release SSA formulation, long-acting OCT (LAR), lanreotide-SR, lanreotide-Autogel, the patient's compliance to SSA therapy was improved and escape from treatment, which was common with the subcutaneous formulation, was avoided. However, rate of objective response was not significantly improved as compared to short-acting SSA. On the other hand, it has to be remarked that long-acting SSA are being used in NET patients at doses correspondent to the low doses of short-acting formulation. The higher commercially available doses of LAR is 30 mg, which is assumed to be comparable to 300 µg of short-acting OCT in the therapy of acromegaly.

Only one study was designed to investigate the use of high-dose LAR (160 mg every 28 days). In this study, objective and hormonal responses in patients with progressive metastatic ileal NET non-responder to standard doses, was significantly elevated. However, this compound has never been commercialized and, of consequence, this first preliminary observation has not been confirmed by further studies.

No systematic studies were performed with the commercially available long-acting SSA used in high-dose treatments. In patients with progressive locally advanced or metastatic NET, increase of the dose or reduction of the interval between injections is a relatively common "empirical" clinical practice, but no studies have been performed to evaluate safety and efficacy of this treatment schedule.

Description:

The patient population will include the patients with a histologically documented diagnosis of WDNET, defined according to the last WHO Classification criteria for NET of gastro-entero-pancreatic, bronchial, thymic or other origin; and showing tumor progression under a standard dose treatment with LAR (30 mg every 28 days) for at least 6 months. Progressive disease will be defined as increased tumor size according to RECIST definitions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2008
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Well differentiated neuroendocrine tumors in disease progression

Exclusion Criteria:

• Well differentiated neuroendocrine tumors without disease progression

• Patients with intolerance to somatostatin analogues

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoid Tumor
• Digestive System Neoplasms
• Endocrine Gland Neoplasms
• Gastrointestinal Neoplasms
• Multiple Endocrine Neoplasia
• Neoplasms
• Neuroendocrine Tumors
• Pancreatic Neoplasms
• Respiratory Tract Neoplasms
• Thymic Neoplasms
• Thymoma
• Thymus Neoplasms

Intervention

Drug:
• Octreotide-LAR
Octreotide-LAR 30 mg administered every 21 days until progression

Locations

Country	Name	City	State
Italy	University Federico II of Naples	Naples

Sponsors (4)

Lead Sponsor	Collaborator
Federico II University	University Hospital, Udine, Italy, University of Genova, University of Perugia, Faculty of Medicine, Department of Internal Medicine

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor stabilization		6 months	No
Secondary	Symptoms improvement		6 months	No
Secondary	Decrease of chromogranin-A		6 months	No