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

A Double Blind, Randomized Placebo Controlled Clinical Trial Investigating the Efficacy and Safety of Somatuline Depot (Lanreotide) Injection in the Treatment of Carcinoid Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Carcinoid Syndrome
• Intervention / Treatment: Drug: Lanreotide; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil
    • Biocancer - Centro de Pesquisa e Tratamento do Câncer
  • Belo Horizonte, Brazil
    • Hospital Lifecenter
  • Belo Horizonte, Brazil
    • Oxion Medicina Oncológica
  • Brasilia, Brazil
    • Hospital Universitário de Brasília
  • Curitiba, Brazil
    • Hospital Erasto Gaertner
  • Porto Alegre, Brazil
    • Irmandade da Santa Casa de Misericordia de Porto Alegre
  • São José do Rio Preto, Brazil
    • Hospital de Base de Sao Jose do Rio Preto
• Czechia
  • Prague, Czechia, 12808
    • VFN Onkologicka klinika
• India
  • Delhi, India
    • Sir Gangaram Hospital
  • Hyderabad, India
    • Indo-American Cancer Institute & Research Centre
  • Hyderabad, India
    • Omega Hospitals
  • Jaipur, India, 302015
    • Santokaba Durlabhji Memorial Hospital and Research Institute
  • Jaipur, India
    • Bhagwan Mahaveer Cancer Hospital and Research Centre
  • Mumbai, India
    • Tata Memorial Hospital
  • Mumbai, India, 422005
    • Shatabdi Super Speciality Hospital
• Latvia
  • Riga, Latvia, 1002
    • Paul Stradins Clinical University hospital
• Poland
  • Wrocław, Poland, 50-367
    • Klinika Endokrynologii, Diabetologii i Leczenia Izotopami
• Russian Federation
  • Moscow, Russian Federation
    • Non-Federal Institution of Healthcare "Central Clinical Hospital # 1 of the LLC "Russian Railways (RZD)"
  • Moscow, Russian Federation
    • Russian Academy of Medical Sciences "Russian Oncological Research Centre named after N.N. Blokhin RAMS"
  • Saint-Petersburg, Russian Federation
    • Federal Institution of Healthcare "Leningradsky Regional Oncological Dispensary"
• Serbia
  • Belgrade, Serbia, 11000
    • Clinic of Endocrinology, diabetes and metabolic diseases, Clinical Center of Serbia
  • Sremska Kamenica, Serbia, 21 204
    • Oncology Institute of Vojvodina, Sremska Kamenica
• South Africa
  • Cape Town, South Africa
    • Groote Schuur Hospital
  • Cape Town, South Africa, 7700
    • Rondebosch Oncology Unit
  • Durban, South Africa
    • Westridge Medical Centre
  • Port Elizabeth, South Africa, 7570
    • GVI Oncology Clinical Trial Unit
• Turkey
  • Kayseri, Turkey, 38039
    • Erciyes University Medical Faculty
• Ukraine
  • Cherkassy, Ukraine
    • Cherkassy Regional Oncology Dispensary
  • Chernivtsi, Ukraine, 58013
    • Chernivtsi Regional Oncology Center
  • Dnepropetrovsk, Ukraine
    • Oncology and Medical Radiology Chair of Dnepropetrovsk State Medical Academy
  • Donetsk, Ukraine
    • Regional Anticancer Center, Department of oncoproctology
  • Kharkiv, Ukraine
    • Municipal Clinical Hospital #2, Proctology department
  • Kyiv, Ukraine
    • National Cancer Institute
  • Kyiv, Ukraine
    • Kyiv City Oncological Hospital, Thoracic department
  • Kyiv, Ukraine
    • Medical Centre "Mriya"
  • Odessa, Ukraine, 65117
    • Odessa regional clinical Hospital
  • Uzhgorod, Ukraine
    • Uzhgorods'ka Tsentral'na Mis'ka Klinichna Likarnya, Mis'kyy Onkologichnyy Tsentr
  • Vinnytsya, Ukraine
    • Vinnytsya Regional Clinical Oncological Center, Vinnytsya State Medical University
• United States
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Health Care System
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
    • West Hollywood, California, United States, 90048
      • Cedars Sinai Outpatient Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Cancer Institute
  • Louisiana
    • Kenner, Louisiana, United States, 70065
      • Louisiana State University Health Science Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 97239
      • University of New Mexico Cancer Care Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Liver Cancer Center
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Eastern Virginia Medical School
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert & Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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]).	Drug: Lanreotide; deep s.c. injection, 120 mg, every 4 weeks (±3 days).; Other Names: Somatuline Depot; Somatuline; Somatuline Autogel; Lanreotide Autogel
Placebo Comparator: 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]).	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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Days With Subcutaneous Octreotide as Rescue Medication	Use of s.c. octreotide required to control symptoms associated with carcinoid syndrome, measured as the percentage of days that s.c. octreotide was used as rescue medication, based on subject Interactive Voice Response System (IVRS) or Interactive Web Response System (IWRS) diary records.	16-week DB phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Frequency of Diarrhoea Events (Per Day) Based on Subject Diary Records.		16-week DB phase
Average Frequency of Flushing Events (Per Day) Based on Subject Diary Records.		16-week DB phase
Percentage of Days of Use of Other Rescue Medication	Usage of other concomitant rescue medications for diarrhoea and/or flushing events, measured as the percentage of days that the medications were used as rescue medication based on subject IVRS/IWRS diary records. Subjects were required to record the use and dose of s.c. octreotide, if any, as well as the use of other concomitant rescue medications (e.g. loperamide 2 mg tabs, and/or tincture of opium).	16-week DB phase
Proportion of Subjects Who Rolled Over Into the IOL Phase Before Completing the DB Phase of the Study	Subjects who rolled over early were those who received less than four DB injections before receiving the first IOL injection.	16-week DB phase
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)	Baseline is defined as the last non-missing observation obtained prior to the initiation of study treatment. Q29 and Q30 range from 1 (Very poor) to 7 (Excellent) with 1 being worst case and 7 the most favourable answer. Scores were derived according to the rules contained within the EORTC scoring manual. All of the scores range in score from 0 to 100. A high score for global health status/QoL represents high QoL. The principle for scoring the scale is: Estimate the average of the items (I1, I2, ..., In) that contribute to the scale; this is the raw score. Raw score = RS = (I1 + I2 +…+ In)/n. For global health status/QoL: Score = {(RS - 1)/range} x 100, where range is the difference between the maximum possible value of RS and the minimum possible value of RS.	Baseline and Week 12 of DB phase
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]	Baseline is defined as the last non-missing observation obtained prior to the initiation of study treatment. The QLQ-G.I.NET21 questionnaire contains 21 single items (Q31 to Q51) which are supplemental items to the EORTC QLQ-C30 questionnaire. Q31 to Q51 range from 1 to 4 with 1 being the most favourable answer and 4 the worst case (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much). Based on these items the scores were generated. All of the scores range in score from 0 to 100. A high score for a symptom scale represents a high level of symptomatology. The principle for scoring the scale is: Estimate the average of the items (I1, I2, ..., In) that contribute to the scale; this is the raw score. RS = (I1 + I2 +…+ In)/n. For symptom scales: Score = {(RS - 1)/range} x 100, where range is the difference between the maximum possible value of RS and the minimum possible value of RS.	Baseline and Week 12 of DB phase
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)	Baseline is defined as the last non-missing observation obtained prior to the initiation of study treatment. The QLQ-G.I.NET21 questionnaire contains 21 single items (Q31 to Q51) which are supplemental items to the EORTC QLQ-C30 questionnaire. Q31 to Q51 range from 1 to 4 with 1 being the most favourable answer and 4 the worst case (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much). Based on these items the scores were generated. All of the scores range in score from 0 to 100. A high score for a symptom scale represents a high level of symptomatology. The principle for scoring the scale is: Estimate the average of the items (I1, I2, ..., In) that contribute to the scale; this is the raw score. RS = (I1 + I2 +…+ In)/n. For symptom scales: Score = {(RS - 1)/range} x 100, where range is the difference between the maximum possible value of RS and the minimum possible value of RS.	Baseline and Week 12 of DB phase
Absolute Changes From Baseline in Biochemical Markers (Plasma Chromogranin A [CgA])	Baseline is defined as the last non-missing observation obtained prior to the initiation of study treatment.	Baseline and Week 12 of DB phase
Absolute Changes From Baseline in Biochemical Markers (Urinary 5-hydroxyindoleacetic Acid [5-HIAA])	Baseline is defined as the last non-missing observation obtained prior to the initiation of study treatment.	Baseline and Week 12 of DB phase

Collaborators and Investigators

• Sponsor: Ipsen

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: October 15, 2008
• First Submitted That Met QC Criteria: October 16, 2008
• First Posted (Estimate): October 17, 2008

Study Record Updates

• Last Update Posted (Actual): October 14, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Diarrhea; Diarrhoea; Neuroendocrine tumour; Flushing; NET; Neuroendocrine tumor; Somatuline Depot; Carcinoid tumor; Lanreotide Autogel; Carcinoid tumour
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Disease; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Drug-Related Side Effects and Adverse Reactions; Syndrome; Carcinoid Tumor; Malignant Carcinoid Syndrome; Serotonin Syndrome; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Lanreotide; Somatostatin
• Other Study ID Numbers: 2-55-52030-730; TR321 (Other Identifier: Tercica Inc); 2010-019066-92 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).