Clinical trial NCT00774930: An Efficacy and Safety Study of Somatuline Depot (Lanreotide) Injection to Treat Carcinoid Syndrome
Official title: A Double Blind, Randomized Placebo Controlled Clinical Trial Investigating the Efficacy and Safety of Somatuline Depot (Lanreotide) Injection in the Treatment of Carcinoid Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoid Syndrome
Keywords: Carcinoid tumor
Somatuline Depot
Lanreotide Autogel
Neuroendocrine tumor
NET
Diarrhea
Flushing
Carcinoid tumour
Neuroendocrine tumour
Diarrhoea
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2008-10-17
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This study consisted of a Screening period, conducted up to 4 months before randomisation, followed by three phases: a 16-week, double blind (DB), randomised, placebo-controlled phase; a 32-week initial open label (IOL) phase; and a long term open label extension (LTOLE) phase.

The DB phase evaluated lanreotide Autogel versus placebo in subjects with a history of carcinoid syndrome (flushing and/or diarrhoea). This was followed by a 32-week IOL phase in which all subjects received lanreotide Autogel 120 mg every 4 weeks. Subjects in countries where lanreotide Autogel had not been approved for the treatment of carcinoid syndrome, who were well-controlled at the end of the 32-week IOL phase and chose to continue to receive lanreotide Autogel, were given the option of participating in a LTOLE phase. The LTOLE phase of the study was planned to end at least 2 years after the last subject had completed his/her participation in the 32-week IOL phase or when marketing approval for the treatment of symptoms of carcinoid syndrome had been obtained in the respective countries (whichever occurred first) or at any time the study was terminated by the Sponsor. The actual overall duration of the study was 6.5 years. During the LTOLE phase all subjects continued to be treated with lanreotide Autogel 120 mg every 4 weeks.

The study planned to enrol approximately 100 adult subjects worldwide. Screening continued until 115 subjects were enrolled in the study.

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).

Primary outcomes:
measure: Percentage of Days With Subcutaneous Octreotide as Rescue Medication
timeFrame: 16-week DB phase
Secondary outcomes:
measure: Average Frequency of Diarrhoea Events (Per Day) Based on Subject Diary Records.
timeFrame: 16-week DB phase
measure: Average Frequency of Flushing Events (Per Day) Based on Subject Diary Records.
timeFrame: 16-week DB phase
measure: Percentage of Days of Use of Other Rescue Medication
timeFrame: 16-week DB phase
measure: Proportion of Subjects Who Rolled Over Into the IOL Phase Before Completing the DB Phase of the Study
timeFrame: 16-week DB phase
measure: Changes From Baseline in "Global Health Status/Quality of Life (QoL)" Score (Based on Items 29 and 30 of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-QLQ] C30)
timeFrame: Baseline and Week 12 of DB phase
measure: Changes From Baseline in "Gastrointestinal (G.I). Symptoms" Subscore (Based on Items Q34, Q35, Q36, Q37 and Q38 of EORTC G.I. Neuroendocrine Tumour [NET] 21]
timeFrame: Baseline and Week 12 of DB phase
measure: Changes From Baseline in QoL in "Endocrine Symptoms" Subscore (Assessed Based on Items Q31, Q32 and Q33 Using EORTC QLQ-G.I.NET-21 Questionnaires)
timeFrame: Baseline and Week 12 of DB phase
measure: Absolute Changes From Baseline in Biochemical Markers (Plasma Chromogranin A [CgA])
timeFrame: Baseline and Week 12 of DB phase
measure: Absolute Changes From Baseline in Biochemical Markers (Urinary 5-hydroxyindoleacetic Acid [5-HIAA])
timeFrame: Baseline and Week 12 of DB phase
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Health Care System
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: West Hollywood
country: United States
facility: Cedars Sinai Outpatient Cancer Center
state: California
city: Louisville
country: United States
facility: Kentuckiana Cancer Institute
state: Kentucky
city: Kenner
country: United States
facility: Louisiana State University Health Science Center
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Care Center
state: New Mexico
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Liver Cancer Center
state: Pennsylvania
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin
state: Wisconsin
city: Belo Horizonte
country: Brazil
facility: Biocancer - Centro de Pesquisa e Tratamento do Câncer
city: Belo Horizonte
country: Brazil
facility: Hospital LifeCenter
city: Belo Horizonte
country: Brazil
facility: Oxion Medicina Oncológica
city: Brasilia
country: Brazil
facility: Hospital Universitário de Brasilia
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
city: São José do Rio Preto
country: Brazil
facility: Hospital de Base de São José do Rio Preto
city: Prague
country: Czechia
facility: VFN Onkologicka klinika
city: Delhi
country: India
facility: Sir Gangaram Hospital
city: Hyderabad
country: India
facility: Indo-American Cancer Institute & Research Centre
city: Hyderabad
country: India
facility: Omega Hospitals
city: Jaipur
country: India
facility: Santokaba Durlabhji Memorial Hospital and Research Institute
city: Jaipur
country: India
facility: Bhagwan Mahaveer cancer hospital and research centre
city: Mumbai
country: India
facility: Shatabdi Super Speciality hospital
city: Mumbai
country: India
facility: Tata Memorial Hospital
city: Riga
country: Latvia
facility: Paul Stradins Clinical University Hospital
city: Wrocław
country: Poland
facility: Klinika Endokrynologii, Diabetologii i Leczenia Izotopami
city: Moscow
country: Russian Federation
facility: Non-Federal Institution of Healthcare "Central Clinical Hospital # 1 of the LLC "Russian Railways (RZD)"
city: Moscow
country: Russian Federation
facility: Russian Academy of Medical Sciences "Russian Oncological Research Centre named after N.N. Blokhin RAMS"
city: Saint-Petersburg
country: Russian Federation
facility: Federal Institution of Healthcare "Leningradsky Regional Oncological Dispensary"
city: Belgrade
country: Serbia
facility: Clinic of Endocrinology, diabetes and metabolic diseases, Clinical Center of Serbia
city: Sremska Kamenica
country: Serbia
facility: Oncology Institute of Vojvodina, Sremska Kamenica
city: Cape Town
country: South Africa
facility: Rondebosch Oncology Unit
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
city: Durban
country: South Africa
facility: Westridge Medical Centre
city: Port Elizabeth
country: South Africa
facility: GVI Oncology Clinical Trial Unit
city: Kayseri
country: Turkey
facility: Erciyes University Medical Faculty
city: Cherkassy
country: Ukraine
facility: Cherkassy Regional Oncology Dispensary
city: Chernivtsi
country: Ukraine
facility: Chernivtsi Regional Oncology Center
city: Dnepropetrovsk
country: Ukraine
facility: Oncology and Medical Radiology Chair of Dnepropetrovsk State Medical Academy
city: Donetsk
country: Ukraine
facility: Regional Anticancer Center, Department of oncoproctology
city: Kharkiv
country: Ukraine
facility: Municipal Clinical Hospital #2, Proctology department
city: Kyiv
country: Ukraine
facility: Kyiv City Oncological Hospital, Thoracic department
city: Kyiv
country: Ukraine
facility: Medical Centre "Mriya"
city: Kyiv
country: Ukraine
facility: National Cancer Institute
city: Odessa
country: Ukraine
facility: Odessa Regional Clinical Hospital
city: Uzhgorod
country: Ukraine
facility: Uzhgorods'ka Tsentral'na Mis'ka Klinichna Likarnya, Mis'kyy Onkologichnyy Tsentr
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Clinical Oncological Center, Vinnytsya State Medical University
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
citation: Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA; ELECT Study Group *. EVALUATION OF LANREOTIDE DEPOT/AUTOGEL EFFICACY AND SAFETY AS A CARCINOID SYNDROME TREATMENT (ELECT): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL. Endocr Pract. 2016 Sep;22(9):1068-80. doi: 10.4158/EP151172.OR. Epub 2016 May 23.
citation: Blot K, Duchateau L, Lescrauwaet B, Liyanage N, Ray D, Mirakhur B, Vinik AI. A Patient-Reported Outcomes Analysis Of Lanreotide In The Treatment Of NETs Patients With Carcinoid Syndrome: Evidence From The ELECT Trial. Patient Relat Outcome Meas. 2019 Oct 29;10:335-343. doi: 10.2147/PROM.S219982. eCollection 2019.