An Efficacy and Safety Study of Somatuline Depot (Lanreotide) Injection to Treat Carcinoid Syndrome
- Registration Number
- NCT00774930
- Lead Sponsor
- Ipsen
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 115
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo (DB) and lanreotide Autogel 120 mg in IOL and LTOLE Placebo 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 \[whichever occurred first\]). Lanreotide Autogel (Somatuline Depot) 120 mg Lanreotide 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 \[whichever occurred first\]).
- Primary Outcome Measures
Name Time Method Percentage of Days With Subcutaneous Octreotide as Rescue Medication 16-week DB phase 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.
- Secondary Outcome Measures
Name Time Method Percentage of Days of Use of Other Rescue Medication 16-week DB phase 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).
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 and Week 12 of DB phase 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.Absolute Changes From Baseline in Biochemical Markers (Plasma Chromogranin A [CgA]) Baseline and Week 12 of DB phase Baseline is defined as the last non-missing observation obtained prior to the initiation of study treatment.
Average Frequency of Diarrhoea Events (Per Day) Based on Subject Diary Records. 16-week DB phase Absolute Changes From Baseline in Biochemical Markers (Urinary 5-hydroxyindoleacetic Acid [5-HIAA]) Baseline and Week 12 of DB phase Baseline is defined as the last non-missing observation obtained prior to the initiation of study treatment.
Average Frequency of Flushing Events (Per Day) Based on Subject Diary Records. 16-week DB phase Proportion of Subjects Who Rolled Over Into the IOL Phase Before Completing the DB Phase of the Study 16-week DB phase Subjects who rolled over early were those who received less than four DB injections before receiving the first IOL injection.
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 and Week 12 of DB phase 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.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 and Week 12 of DB phase 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.
Trial Locations
- Locations (54)
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
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