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”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2007

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.

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Octreotide-LAR
  • Patients will receive every 21 days an injection of octreotide-LAR 30 mg until progression is documented.

Primary Measures

• Tumor stabilization
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• Symptoms improvement
  • Time Frame: 6 months
    Safety Issue?: No
• Decrease of chromogranin-A
  • Time Frame: 6 months
    Safety Issue?: No

Inclusion Criteria:

• Well differentiated neuroendocrine tumors in disease progression

Exclusion Criteria:

• Well differentiated neuroendocrine tumors without disease progression
• Patients with intolerance to somatostatin analogues

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Federico II University

Overall Clinical Trial Officials and Contacts

Annamaria Colao, MD, PhD Principal Investigator University Federico II of Naples  

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00990535

Study ID Number: NeuroendoUnit-6

ClinicalTrials.gov Identifier: NCT00990535

Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health