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

Carcinoid Syndrome Clinical Trial

— ELECT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00774930
• Other study ID #: 2-55-52030-730
• Secondary ID: TR3212010-019066
• Status: Completed
• Phase: Phase 3
• Start date: May 2009
• Est. completion date: December 2015

Study information

• Verified date: September 2022
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: December 2015
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoid Syndrome
• Carcinoid Tumor
• Malignant Carcinoid Syndrome
• Serotonin Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
Brazil	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	Brasilia
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
Czechia	VFN Onkologicka klinika	Prague
India	Sir Gangaram Hospital	Delhi
India	Indo-American Cancer Institute & Research Centre	Hyderabad
India	Omega Hospitals	Hyderabad
India	Bhagwan Mahaveer cancer hospital and research centre	Jaipur
India	Santokaba Durlabhji Memorial Hospital and Research Institute	Jaipur
India	Shatabdi Super Speciality hospital	Mumbai
India	Tata Memorial Hospital	Mumbai
Latvia	Paul Stradins Clinical University Hospital	Riga
Poland	Klinika Endokrynologii, Diabetologii i Leczenia Izotopami	Wroclaw
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"	Moscow
Russian Federation	Federal Institution of Healthcare "Leningradsky Regional Oncological Dispensary"	Saint-Petersburg
Serbia	Clinic of Endocrinology, diabetes and metabolic diseases, Clinical Center of Serbia	Belgrade
Serbia	Oncology Institute of Vojvodina, Sremska Kamenica	Sremska Kamenica
South Africa	Groote Schuur Hospital	Cape Town
South Africa	Rondebosch Oncology Unit	Cape Town
South Africa	Westridge Medical Centre	Durban
South Africa	GVI Oncology Clinical Trial Unit	Port Elizabeth
Turkey	Erciyes University Medical Faculty	Kayseri
Ukraine	Cherkassy Regional Oncology Dispensary	Cherkassy
Ukraine	Chernivtsi Regional Oncology Center	Chernivtsi
Ukraine	Oncology and Medical Radiology Chair of Dnepropetrovsk State Medical Academy	Dnepropetrovsk
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	Odessa
Ukraine	Uzhgorods'ka Tsentral'na Mis'ka Klinichna Likarnya, Mis'kyy Onkologichnyy Tsentr	Uzhgorod
Ukraine	Vinnytsya Regional Clinical Oncological Center, Vinnytsya State Medical University	Vinnytsya
United States	University of New Mexico Cancer Care Center	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Louisiana State University Health Science Center	Kenner	Louisiana
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	VA Greater Los Angeles Health Care System	Los Angeles	California
United States	Kentuckiana Cancer Institute	Louisville	Kentucky
United States	Froedtert & Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	UPMC Liver Cancer Center	Pittsburgh	Pennsylvania
United States	Oregon Health Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Stanford Cancer Center	Stanford	California
United States	Cedars Sinai Outpatient Cancer Center	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

United States,  Brazil,  Czechia,  India,  Latvia,  Poland,  Russian Federation,  Serbia,  South Africa,  Turkey,  Ukraine, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Average Frequency of Diarrhoea Events (Per Day) Based on Subject Diary Records.		16-week DB phase
Secondary	Average Frequency of Flushing Events (Per Day) Based on Subject Diary Records.		16-week DB phase
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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