An Efficacy and Safety Study of Somatuline Depot (Lanreotide) Injection to Treat Carcinoid Syndrome
Condition: Carcinoid Syndrome
MeSH terms: Carcinoid Tumor; Malignant Carcinoid Syndrome; Syndrome; Serotonin Syndrome
Intervention: Lanreotide; Placebo
Intervention description: deep s.c. injection, 120 mg, every 4 weeks (±3 days).; deep s.c. injection of placebo (0.9% saline solution) every 4 weeks (±3 days) for 16 weeks, then deep s.c. injection of lanreotide 120 mg, every 4 weeks (±3 days).
Intervention MeSH terms: Lanreotide; Somatostatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 115.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Carcinoid tumor; Somatuline Depot; Lanreotide Autogel; Neuroendocrine tumor; NET; Diarrhea; Flushing; Carcinoid tumour; Neuroendocrine tumour; Diarrhoea

Summary:

      The purpose of this study was to determine whether monthly deep subcutaneous (s.c.)
      injections of lanreotide Autogel (Somatuline Depot) were effective and safe in controlling
      diarrhoea and flushing by reducing the usage of s.c. short-acting octreotide as a rescue
      medication to control symptoms in subjects with carcinoid syndrome.
    

Eligibility criteria:

        Subjects were eligible for participation in the study if they met the following criteria:

          1. At least 18 years of age at the time of first dosing.

          2. Subjects must have given signed informed consent before any study related activities
             were conducted.

          3. Subjects in the United States of America (USA) must have given written authorisation
             for the release of protected health information in compliance with the Health
             Insurance Portability and Accountability Act (HIPAA) regulations; subjects in other
             countries must have provided appropriate authorisation as needed by regulatory
             authorities in each country.

          4. Subjects must have been willing to receive s.c. octreotide injections as rescue
             medication, as needed to control their symptoms, if any.

          5. If female, the subject must not have been pregnant (confirmed by negative pregnancy
             test) and must have had the following documented via verbally given history:

               -  At least 1 year postmenopausal (natural cessation of menses), or

               -  Surgically sterile (if by tubal ligation, surgery must have been performed more
                  than 3 months prior to entry into the study), or

               -  If the subject was of childbearing potential and sexually active, she must have
                  been using an acceptable form of contraception (oral, injected, transdermal or
                  implanted contraceptives, diaphragm or barrier method with spermicidal and/or
                  intrauterine device); local methods such as condoms or sponges/vaginal tablets
                  were not acceptable forms of contraception.

          6. Subjects with a histopathologically confirmed diagnosis of carcinoid tumour or, a
             carcinoid tumour of unknown location with liver metastases (documented biopsy), and a
             history of carcinoid syndrome (flushing and/or diarrhoea) who were either naïve to
             treatment with a somatostatin analogue (SSTa) or responsive (according to the opinion
             of the principal investigator) to conventional doses of Sandostatin LAR® Depot (LAR;
             ≤30 mg every 4 weeks) or to daily doses of ≤600 μg of s.c. octreotide.

          7. Confirmation of positive somatostatin receptor (SSTR) status by somatostatin receptor
             scintigraphy (SRS; up to 6 months prior to study entry at the Screening Visit).

          8. Absence of tumour progression documented by two sequential computed tomography (CT)
             scans or two sequential magnetic resonance imaging (MRI) scans (≥3 months apart); the
             last CT or MRI scan must have been performed within 6 months of study entry (Screening
             Visit).

          9. Subjects previously treated with LAR, must have received their last dose of LAR at
             least 4 weeks prior to first dose of study treatment (no later than at the Screening
             Visit).

         10. Be able to communicate and cooperate with the principal investigator and the staff and
             willing to comply with the study instructions.

        Subjects were excluded from entering the study for the following reasons:

          1. History of known allergy or hypersensitivity to investigational drug or any components
             of its formulation, or octreotide.

          2. History of carcinoid syndrome refractory to treatment with conventional doses of SSTa.

          3. Treatment with any other investigational drug within 30 days prior to study entry
             (Screening Visit) and/or at any time during the subject's participation in the study.

          4. Treatment with interferon, chemotherapy and/or radiotherapy (a radiolabelled SSTa)
             and/or tumour debulking <3 months prior to study entry (Screening Visit).

          5. History of hepatic arterial embolisation, hepatic arterial chemoembolisation and/or
             selective internal radiation therapy (selective internal radiation [SIR] therapy
             [SIRT]; e.g. SIR Spheres) <6 months prior to study entry (Screening Visit).

          6. Short bowel syndrome.

          7. Uncontrolled diabetes and/or hypertension.

          8. Severe renal impairment (glomerular filtration rate <30 mL/min/1.73 m2) and/or severe
             liver impairment as evidenced by serum total bilirubin >1.5 mg/dL associated with bile
             duct blockage or with alkaline phosphatase (ALP), aspartate aminotransferase (AST) or
             alanine aminotransferase (ALT) >5.0 upper limit of normal (ULN).

          9. Diagnosis of cardiac disease New York Heart Association (NYHA) functional
             classification >Class I. (Subject has limitation of physical activity. Ordinary
             physical activity causes undue fatigue, palpitation, or dyspnoea).

         10. Life expectancy less than 1 year.

         11. Any malignancies except carcinoid tumour, basocellular carcinoma of the skin, in situ
             carcinoma of the cervix and ≥5 years disease free after curative cancer treatment.

         12. Any serious medical condition that could jeopardise the safety of the subject and/or
             the efficacy assessments of the study.

         13. Subject is being treated with a proton pump inhibitor (PPI) and has been at a stable
             dose (no change in dose or frequency of administration) for less than 4 weeks at study
             entry (Screening Visit).