Clinical Trial Results:
A PHASE II, MULTICENTRE, RANDOMIZED CONTROLLED STUDY EVALUATING THE QUALITY OF LIFE IN PATIENTS WITH INOPERABLE MALIGNANT BOWEL OBSTRUCTION TREATED WITH LANREOTIDE AUTOGEL 120 MG IN COMBINATION WITH STANDARD CARE VS. STANDARD CARE ALONE (QOL IN IMBO STUDY)
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Summary
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EudraCT number |
2013-003176-12 |
Trial protocol |
IT |
Global end of trial date |
16 Jan 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jun 2019
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First version publication date |
29 Jun 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
A-93-52030-279
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02365584 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Ipsen SpA
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Sponsor organisation address |
Via del Bosco Rinnovato, 6, Milano Fiori Nord, Palazzo U7, Milano, Italy, 20090 Assago
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Public contact |
Medical Director, Ipsen SpA, clinical.trials@ipsen.com
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Scientific contact |
Medical Director, Ipsen SpA, clinical.trials@ipsen.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Jan 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Jan 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the impact on Quality of Life (Edmonton Symptom Assessment System [ESAS] total score) of lanreotide Autogel 120 milligrams (mg) in combination with standard care, in comparison to standard care alone, in patients affected by inoperable malignant bowel obstruction.
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Protection of trial subjects |
The study was conducted under the provisions of the Declaration of Helsinki, in accordance with the International Conference on Harmonisation Consolidated Guideline on Good Clinical Practice and in compliance with Independent Ethics Committees / Institutional Review Boards and informed consent regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Jan 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 43
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Worldwide total number of subjects |
43
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EEA total number of subjects |
43
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
29
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From 65 to 84 years |
12
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85 years and over |
2
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Recruitment
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Recruitment details |
Recruitment to this prospective, randomised, parallel arm, open-label study began on 14 Jan 2015. Patients with a documented diagnosis of inoperable malignant bowel obstruction who had a nasogastric tube (NGT) or presented with ≥ 3 vomiting episodes/day in the last consecutive 48 hours at time of enrolment were recruited to 14 centres in Italy. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Overall, 43 patients were enrolled and treated in this phase II study. Planned study period duration was 28 days. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Standard Care | |||||||||||||||||||||
Arm description |
Patients received standard care only according to site clinical practice. | |||||||||||||||||||||
Arm type |
Standard Care | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Standard Care + Lanreotide Autogel | |||||||||||||||||||||
Arm description |
Patients received standard care according to site clinical practice and a single administration of Lanreotide Autogel 120 mg by deep subcutaneous injection on Day 1. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Lanreotide Autogel
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Investigational medicinal product code |
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Other name |
Somatuline Autogel
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Lanreotide Autogel was administered by deep subcutaneous injection in the upper outer quadrant of the buttock. Administration of Lanreotide Autogel was to occur in conjunction with or on the same day of standard care therapy administration. The administrations were supervised by the Investigator, or designee.
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Baseline characteristics reporting groups
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Reporting group title |
Standard Care
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Reporting group description |
Patients received standard care only according to site clinical practice. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard Care + Lanreotide Autogel
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Reporting group description |
Patients received standard care according to site clinical practice and a single administration of Lanreotide Autogel 120 mg by deep subcutaneous injection on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Standard Care
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Reporting group description |
Patients received standard care only according to site clinical practice. | ||
Reporting group title |
Standard Care + Lanreotide Autogel
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Reporting group description |
Patients received standard care according to site clinical practice and a single administration of Lanreotide Autogel 120 mg by deep subcutaneous injection on Day 1. | ||
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End point title |
Mean Area Under Curve (AUC) of Edmonton Symptom Assessment System (ESAS) Total Scores Collected for the First 7 Days; Full Analysis Set (FAS) | ||||||||||||
End point description |
Quality of Life was assessed using ESAS, evaluating 9 common symptoms in cancer patients: pain, activity, nausea, depression, anxiety, drowsiness, appetite, well-being and shortness of breath. Symptom severity is rated 0-10 on a numerical scale (0=symptom absent; 10=worst severity). ESAS total score is sum of the 9 items (max score=90). Low scores indicate good quality of life; high scores indicate strong discomfort. Questionnaire assessments by the patient or by nurse/caregiver in case of patient’s physical inability. AUC is area under the line which joins the points defined by plotting ESAS total score on vertical axis and time values on horizontal axis, computed using trapezoidal rule.
Primary endpoint was analysed using the FAS which included all randomised patients who received study therapy, fulfilled the ESAS questionnaire at baseline and had ≥ 5 post-treatment assessments during first 7 days. Mean AUC of ESAS total scores during first 7 days is presented.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1, before randomisation), Days 2, 3, 4, 5, 6 and 7.
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Statistical analysis title |
ESAS AUC: treatment comparison | ||||||||||||
Statistical analysis description |
Analysis of covariance (ANCOVA), where the AUC was the dependent and the independent was the baseline ESAS total score.
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Comparison groups |
Standard Care v Standard Care + Lanreotide Autogel
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Number of subjects included in analysis |
38
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
= 0.5396 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Adjusted Least Square Mean Difference | ||||||||||||
Point estimate |
-11
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-47 | ||||||||||||
upper limit |
25 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
17.7
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| Notes [1] - The assumptions required for the analysis of covariance (ANCOVA) were to be tested as follows: • The equality of variances was to verified using the Levene’s test. If it was significant AUC values were to be properly transformed. • The linear relationship of AUC with the basal total score within treatment group was to be tested by a regression analysis. • The parallelism of the regression lines between groups and the slope non zero value with the appropriate F tests. |
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End point title |
Mean Change From Baseline in ESAS Total Score; FAS | |||||||||||||||||||||
End point description |
Quality of Life was assessed using ESAS, evaluating 9 common symptoms in cancer patients: pain, activity, nausea, depression, anxiety, drowsiness, appetite, well-being and shortness of breath. Symptom severity is rated 0-10 on a numerical scale (0=symptom absent; 10=worst severity). ESAS total score is sum of the 9 items (max score=90). Low scores indicate good quality of life; high scores indicate strong discomfort. Questionnaire assessments by the patient or by nurse/caregiver in case of patient’s physical inability.
Secondary endpoints were analysed using the ITT population but to permit following the FAS which was used for primary endpoint analysis, ESAS total score results are reported for both the ITT and the FAS. Mean change from baseline of ESAS total score at Days 7, 14 and 28 is presented here for the FAS; a positive change indicates a worsening condition. 'n' in category title indicates number of patients analysed at each time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1, before randomisation) and Days 7, 14 and 28.
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Mean Change From Baseline in ESAS Total Score; Intention To Treat (ITT) Population | |||||||||||||||||||||
End point description |
Quality of Life was assessed using ESAS, evaluating 9 common symptoms in cancer patients: pain, activity, nausea, depression, anxiety, drowsiness, appetite, well-being and shortness of breath. Symptom severity is rated 0-10 on a numerical scale (0=symptom absent; 10=worst severity). ESAS total score is sum of the 9 items (max score=90). Low scores indicate good quality of life; high scores indicate strong discomfort. Questionnaire assessments by the patient or by nurse/caregiver in case of patient’s physical inability.
Secondary endpoints were analysed using the ITT population but to permit following the FAS which was used for primary endpoint analysis, ESAS total score results are reported for both the ITT and the FAS. Mean change from baseline of ESAS total score at Days 7, 14 and 28 is presented here for the ITT population (all randomised patients); a positive change indicates a worsening condition. 'n' in category title indicates number of patients analysed at each time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1, before randomisation) and Days 7, 14 and 28.
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Mean Change From Baseline in Single ESAS Items Symptom Scores; ITT Population | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Quality of Life was assessed using ESAS, evaluating 9 common symptoms in cancer patients: pain, activity, nausea, depression, anxiety, drowsiness, appetite, well-being and shortness of breath. Symptom severity is rated 0-10 on a numerical scale (0=symptom absent; 10=worst severity). Low scores indicate good quality of life; high scores indicate strong discomfort. Questionnaire assessments by the patient or by nurse/caregiver in case of patient’s physical inability.
Mean change from baseline of each individual ESAS item score at Days 7, 14 and 28 is presented for the ITT population (all randomised patients); a positive change indicates a worsening condition. 'n' in category title indicates number of patients analysed at each time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1, before randomisation) and Days 7, 14 and 28.
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Mean Change From Baseline in Performing General Activity (Karnofsky Performance Status [KPS]); ITT Population | |||||||||||||||||||||
End point description |
The KPS allows patients to be classified as to their functional impairment and was used to assess general activity. KPS scores range from 0 (dead) to 100 (normal/no disease) and are classified as 0-40 = unable to care for self; 50-70 = unable to work; 80-100 = able to work. The lower the KPS score, the worse the survival for most serious illnesses. Scores were recorded on the patient’s medical file at each study visit (Days 1, 7, 14 and 28).
Mean change from baseline of KPS score at Days 7, 14 and 28 is presented for the ITT population (all randomised patients); a negative change indicates a worsening condition. 'n' in category title indicates number of patients analysed at each time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1, before randomisation) and Days 7, 14 and 28.
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Mean Change From Baseline in Daily Intensity of Abdominal Pain Score (Visual Analogue Scale [VAS]); ITT Population | |||||||||||||||||||||
End point description |
Abdominal pain was assessed using the VAS numeric pain distress scale which is a 100-millimetre (10-centimetre) scoring scale on which patients mark their perceived level of pain. Scores range from 0 to 100 where 0=no pain and 100=unbearable pain. Higher scores indicate a worse outcome. Scores were recorded on the Patient Diary daily until the end of study (Day 28), by the patient or filled in by the nurse/caregiver in case of patient’s physical inability.
Mean change from baseline of VAS for abdominal pain at Days 7, 14 and 28 is presented for the ITT population (all randomised patients); a positive change indicates a worsening condition. 'n' in category title indicates number of patients analysed at each time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1, before randomisation) and Days 7, 14 and 28.
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Number of Patients Experiencing ≤ 2 Vomiting Episodes/Day During at Least 3 Consecutive Days, in Patients Without NGT | |||||||||||||||||||||||||||
End point description |
Vomiting episodes and NGT presence were recorded on the Patient Diary daily until the end of study (Day 28), by the patient or filled in by the nurse/caregiver in case of patient’s physical inability. Number of patients experiencing ≤ 2 vomiting episodes/day during at least 3 consecutive days, in patients without NGT, is presented for the ITT population (all randomised patients). Number of patients without NGT for each of the specified time points is also presented. Patients without NGT were defined as patients without the insertion of NGT for the whole study period.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1, before randomisation) to Days 7, 14 and 28.
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Mean Daily NGT Secretion Volume, in Patients With a NGT | ||||||||||||||||||||||||
End point description |
NGT presence and related secretion volume were recorded on the Patient Diary daily until the end of study (Day 28), by the patient or filled in by the nurse/caregiver in case of patient’s physical inability. Mean daily secretion volumes, in patients with NGT, is presented. Only in patients with NGT were included in the analysis (Standard Care arm: n=11, 15, 16 and 16 at Baseline, Days 7, 14 and 28, respectively; Standard Care + Lanreotide Autogel arm: n=14, 14, 15 and 15 at Baseline, Days 7, 14 and 28, respectively). 'n' in category title indicates number of patients with data available for analysis at each time point; 999999 denotes a data value as non-calculable.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1, before randomisation) and Days 7, 14 and 28.
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Mean Change From Baseline in Number of Daily Vomiting Episodes; ITT Population | |||||||||||||||||||||
End point description |
Vomiting episodes were recorded on the Patient Diary daily until the end of study (Day 28), by the patient or filled in by the nurse/caregiver in case of patient’s physical inability. Mean change from baseline in number of daily vomiting episodes for the periods Day 1 to Day 7, Day 1 to Day 14 and Day 1 to Day 28 is presented for the ITT population (all randomised patients). 'n' in category title indicates number of patients with data available for analysis at each time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1, before randomisation) and Days 7, 14 and 28.
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Assessment of Passage of Stools; ITT Population | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Passage of stools assessments (Yes/No) were recorded on the Patient Diary daily until the end of study (Day 28), by the patient or filled in by the nurse/caregiver in case of patient’s physical inability.
The ITT population included all randomised patients.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 1, before randomisation) to Day 28.
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From baseline (Day 1) until end of study (Day 28).
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Adverse event reporting additional description |
Treatment emergent adverse events are reported for the safety population which included all patients who received at least one dose of study therapy.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Standard Care
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Reporting group description |
Patients received standard care only according to site clinical practice. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard Care + Lanreotide Autogel
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Reporting group description |
Patients received standard care according to site clinical practice and a single administration of Lanreotide Autogel 120 mg by deep subcutaneous injection on Day 1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was terminated early due to insufficient recruitment. As a consequence, the results of the analyses should be interpreted cautiously and no conclusions should be made. | |||
