An Efficacy and Safety Study of Somatuline Depot (Lanreotide) Injection to Treat Carcinoid Syndrome

NCT ID: NCT00774930

Last Updated: 2022-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2015-12-31

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.

Conditions

Carcinoid Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lanreotide Autogel (Somatuline Depot) 120 mg

Subjects received deep s.c. lanreotide Autogel 120 mg every 4 weeks (±3 days) for 16 weeks (DB phase).

After completing the DB phase (or if they met criteria for early roll over [ERO]) the subjects entered the IOL phase during which they received lanreotide Autogel 120 mg deep s.c. every 4 weeks for 32 weeks. During the LTOLE phase, subjects continued treatment with lanreotide Autogel 120 mg deep s.c. every 4 weeks until at least 2 years after the last subject completed the IOL phase or when marketing approval for the treatment of symptoms of carcinoid syndrome was obtained [whichever occurred first]).

Group Type: EXPERIMENTAL

Lanreotide

Intervention Type: DRUG

deep s.c. injection, 120 mg, every 4 weeks (±3 days).

Placebo (DB) and lanreotide Autogel 120 mg in IOL and LTOLE

Subjects received deep s.c. placebo every 4 weeks (±3 days) for 16 weeks (DB phase).

After completing the DB phase (or if they met criteria for ERO) the subjects entered the IOL phase during which they received lanreotide Autogel 120 mg deep s.c. every 4 weeks for 32 weeks. During the LTOLE phase, subjects continued treatment with lanreotide Autogel 120 mg deep s.c. every 4 weeks until at least 2 years after the last subject completed the IOL phase or when marketing approval for the treatment of symptoms of carcinoid syndrome was obtained [whichever occurred first]).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Interventions

Lanreotide

deep s.c. injection, 120 mg, every 4 weeks (±3 days).

Intervention Type: DRUG

Placebo

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 Type: DRUG

Other Intervention Names

Somatuline; Somatuline Depot; Somatuline Autogel; Lanreotide Autogel

Eligibility Criteria

Inclusion 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ipsen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

VA Greater Los Angeles Health Care System

Los Angeles, California, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Stanford Cancer Center

Stanford, California, United States

Cedars Sinai Outpatient Cancer Center

West Hollywood, California, United States

Kentuckiana Cancer Institute

Louisville, Kentucky, United States

Louisiana State University Health Science Center

Kenner, Louisiana, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

University of New Mexico Cancer Care Center

Albuquerque, New Mexico, United States

Providence Portland Medical Center

Portland, Oregon, United States

Oregon Health Science University

Portland, Oregon, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

UPMC Liver Cancer Center

Pittsburgh, Pennsylvania, United States

Eastern Virginia Medical School

Norfolk, Virginia, United States

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Biocancer - Centro de Pesquisa e Tratamento do Câncer

Belo Horizonte, , Brazil

Hospital LifeCenter

Belo Horizonte, , Brazil

Oxion Medicina Oncológica

Belo Horizonte, , Brazil

Hospital Universitário de Brasilia

Brasília, , Brazil

Hospital Erasto Gaertner

Curitiba, , Brazil

Irmandade da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, , Brazil

Hospital de Base de São José do Rio Preto

São José do Rio Preto, , Brazil

VFN Onkologicka klinika

Prague, , Czechia

Sir Gangaram Hospital

Delhi, , India

Indo-American Cancer Institute & Research Centre

Hyderabad, , India

Omega Hospitals

Hyderabad, , India

Santokaba Durlabhji Memorial Hospital and Research Institute

Jaipur, , India

Bhagwan Mahaveer cancer hospital and research centre

Jaipur, , India

Shatabdi Super Speciality hospital

Mumbai, , India

Tata Memorial Hospital

Mumbai, , India

Paul Stradins Clinical University Hospital

Riga, , Latvia

Klinika Endokrynologii, Diabetologii i Leczenia Izotopami

Wroclaw, , Poland

Non-Federal Institution of Healthcare "Central Clinical Hospital # 1 of the LLC "Russian Railways (RZD)"

Moscow, , Russia

Russian Academy of Medical Sciences "Russian Oncological Research Centre named after N.N. Blokhin RAMS"

Moscow, , Russia

Federal Institution of Healthcare "Leningradsky Regional Oncological Dispensary"

Saint Petersburg, , Russia

Clinic of Endocrinology, diabetes and metabolic diseases, Clinical Center of Serbia

Belgrade, , Serbia

Oncology Institute of Vojvodina, Sremska Kamenica

Kamenitz, , Serbia

Rondebosch Oncology Unit

Cape Town, , South Africa

Groote Schuur Hospital

Cape Town, , South Africa

Westridge Medical Centre

Durban, , South Africa

GVI Oncology Clinical Trial Unit

Port Elizabeth, , South Africa

Erciyes University Medical Faculty

Kayseri, , Turkey (Türkiye)

Cherkassy Regional Oncology Dispensary

Cherkassy, , Ukraine

Chernivtsi Regional Oncology Center

Chernivtsi, , Ukraine

Oncology and Medical Radiology Chair of Dnepropetrovsk State Medical Academy

Dnipro, , Ukraine

Regional Anticancer Center, Department of oncoproctology

Donetsk, , Ukraine

Municipal Clinical Hospital #2, Proctology department

Kharkiv, , Ukraine

Kyiv City Oncological Hospital, Thoracic department

Kyiv, , Ukraine

Medical Centre "Mriya"

Kyiv, , Ukraine

National Cancer Institute

Kyiv, , Ukraine

Odessa Regional Clinical Hospital

Odesa, , Ukraine

Uzhgorods'ka Tsentral'na Mis'ka Klinichna Likarnya, Mis'kyy Onkologichnyy Tsentr

Uzhhorod, , Ukraine

Vinnytsya Regional Clinical Oncological Center, Vinnytsya State Medical University

Vinnytsia, , Ukraine

Countries

United States; Brazil; Czechia; India; Latvia; Poland; Russia; Serbia; South Africa; Turkey (Türkiye); Ukraine

References

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.

Reference Type: RESULT

PMID: 27214300 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31754316 (View on PubMed)

Other Identifiers

TR321

Identifier Type: OTHER

Identifier Source: secondary_id

2010-019066-92

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2-55-52030-730

Identifier Type: -

Identifier Source: org_study_id