Intestinal Obstruction
Conditions
Brief summary
To assess the efficacy of Lanreotide Autogel 120 mg for the relief of vomiting due to inoperable malignant intestinal obstruction in patients without nasogastric tube (NGT) and to assess the efficacy of lanreotide Autogel 120 mg on removal of nasogastric tube without the recurrence of vomiting in patients with an inoperable malignant intestinal obstruction with a nasogastric tube.
Interventions
120mg administered via deep subcutaneous injection at Day 0 and Day 28.
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent before any study related procedure * Male and female patients age 18 years or older at time of enrollment * Diagnosis of intestinal obstruction of malignant origin * In case of peritoneal carcinomatosis, confirmation by CT or MRI scan within the 3 months preceding the inclusion in the study * Confirmed as inoperable after surgical advice * Patient with a nasogastric tube OR presenting with 3 or more episodes of vomiting / 24h in the last 48 hours * Estimated life expectancy 1 month or more
Exclusion criteria
* Operable obstruction or subobstruction * Bowel obstruction due to a non-malignant cause * Signs of bowel perforation * Prior treatment with somatostatin or any other analogue within the previous 60 days * A known hypersensitivity to any of the study treatments or related compounds * Previous participation in this study * Is likely to require treatment during the study with drugs that are not permitted by the study protocol * Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the subject's safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders Before or at Day 7 | From Day 0 to Day 7 | The primary endpoint assessed the percentage of responding subjects before or at Day 7. A responder was defined as a subject experiencing ≤2 vomiting episodes/day during at least 3 consecutive days at any timepoint between Day 0 and Day 7 (for subjects without NGT at baseline), or as a subject in whom the NGT had been removed during at least 3 consecutive days at any timepoint between Day 0 and Day 7 without vomiting recurrence (for subjects with NGT at baseline), as recorded on diary cards which were completed every day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time Between First Lanreotide Autogel® Injection and Clinical Response in Phase 1 | From Day 0 to Day 28 | The time for clinical response in Phase 1 (up to Day 28) was defined as the time from inclusion (Day 0) to the date of clinical response. A response was defined as occurrence of ≤ 2 vomiting episodes/day for at least 3 consecutive days at any timepoint between Day 0 and Day 28 (for patients without NGT use at baseline) or the removal of NGT for at least 3 consecutive days at any timepoint between Day 0 and Day 28 without vomiting recurrence (for patients with NGT use at baseline). The Kaplan-Meier estimate of median time to clinical response are presented. |
| Median Change From Baseline in Quality of Life as Assessed by Edmonton Symptom Assessment System (ESAS) in Phase 1 | Days 0, 7, 14 and 28 | Quality of Life was assessed by both subject and investigator based on the ESAS. The ESAS scale evaluates 9 symptoms common in cancer subjects: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath. The severity at the time of assessment of each symptom is rated from 0 to 10 on a numerical scale; 0 = symptom is absent and 10 = worst possible severity. Each symptom rating was interpreted independently and a total symptom distress score was calculated for both subject and investigator assessed scores as the sum of the 9 items. Median change from baseline (Day 0) in total symptom distress score, at each of the Phase 1 timepoints is presented and a positive change indicates a worsening condition. |
| Median Change From Baseline in General Activity as Assessed by the Karnofsky Performance Status (KPS) Scale in Phase 1 | Days 0, 7, 14 and 28 | The KPS scale was used to quantify subject's general well-being and activities of daily life. Subjects were classified based on their functional impairment and KPS scores range from 0 (death) to 100 (no evidence of disease). KPS scores are classified as 0-40 = unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly; 50-70 = unable to work; able to live at home and care for most personal needs; varying amount of assistance needed; 80-100 = able to carry on normal activity and to work; no special care needed. Median change from baseline (Day 0) at each of the Phase 1 timepoints is presented and a negative change indicates a worsening condition. |
| Percentage of Responders in Phase 1 | From Day 0 to Day 28 | This endpoint assessed the overall percentage of responding subjects at the Phase 1 timepoints of Days 14 and 28. A responder was defined as a subject experiencing ≤ 2 vomiting episodes/day during at least 3 consecutive days at any timepoint between Day 0 and Days 14 or 28 (for subjects without NGT at baseline) or as a subject in whom the NGT has been removed, during at least 3 consecutive days without vomiting recurrence, at any timepoint between Day 0 and Days 14 and 28 (for subjects with NGT at baseline), as recorded on diary cards which were completed every day. |
| Median Change From Baseline in Abdominal Pain Scores Assessed Using Visual Analogue Scale (VAS) in Phase 1 | Days 0, 7, 14 and 28 | Abdominal pain was assessed using the VAS numeric pain distress scale. The VAS is a 100-millimetre (10-centimetre) scoring scale on which subjects marked on their perceived level of pain. Score range on VAS is from 0 to 100 where 0 = no pain and 100 = unbearable pain. Median change from baseline (Day 0) at each of the Phase 1 timepoints is presented and a positive change indicates a worsening condition. |
| Percentage of Responders Before or at Phase 2 Timepoints | From Day 0 to Day 56 | This endpoint assessed the overall percentage of subjects continuing from Phase 1 and confirmed as a responder at the end of Phase 1, showing a continued response at Days 35, 42 and 56. A responder was defined as a subject experiencing ≤2 vomiting episodes/day during at least 3 consecutive days at any timepoint between Day 0 and Days 35, 42, 56 (for subjects without NGT at baseline), or as a subject in whom the NGT had been removed during at least 3 consecutive days at any timepoint between Day 0 and Days 35, 42, 56 without vomiting recurrence (for subjects with NGT at baseline), as recorded on diary cards which were completed every day. |
| Median Change From Baseline in Quality of Life as Assessed by ESAS in Phase 2 | Days 0, 35, 42 and 56 | Quality of Life was assessed by both subject and investigator based on the ESAS. The ESAS scale evaluates 9 symptoms common in cancer subjects: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath. The severity at the time of assessment of each symptom is rated from 0 to 10 on a numerical scale, 0 = symptom is absent and 10 = worst possible severity. Each symptom rating was interpreted independently and a total symptom distress score was calculated for both subject and investigator assessed scores as the sum of the 9 items. Median change from baseline (Day 0) in total symptom distress score, at each of the Phase 2 timepoints is presented and a positive change indicates a worsening condition. |
| Median Change From Baseline in Number of Daily Episodes of Nausea in Phase 1 | Days 0, 7, 14 and 28 | The mean number of daily episodes of nausea were calculated as the sum of episodes of nausea reported the last 3 days before the corresponding visit, divided by 3. The median change from baseline (Day 0) at each of the Phase 1 timepoints is presented and positive change indicates a worsening condition. |
Countries
Belgium
Participant flow
Recruitment details
Subjects diagnosed with inoperable malignant intestinal obstruction were recruited into this single arm, open label study in 15 study centres in Belgium between November 2014 and November 2017.
Pre-assignment details
Overall, 52 subjects were enrolled into this 2 phase study.
Participants by arm
| Arm | Count |
|---|---|
| Lanreotide Autogel® 120 mg - All Subjects All subjects were administered an initial injection of lanreotide Autogel® 120 mg via subcutaneous injection at Day 0 (Phase 1).
Subjects who completed the 28 days of Phase 1 and who were responders as defined by the protocol, had the opportunity to enter Phase 2 and receive a second subcutaneous injection of lanreotide Autogel® 120 mg.
All subjects continued to receive standard of care throughout the study. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 15 |
| Overall Study | Disease progression (death) | 1 |
| Overall Study | Does not meet entry criteria | 1 |
| Overall Study | Ineligible to start Phase 2 | 4 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Reason not specified | 5 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Lanreotide Autogel® 120 mg - All Subjects |
|---|---|
| Age, Continuous | 66.6 years STANDARD_DEVIATION 12.1 |
| Age, Customized 40-49 years | 3 Participants |
| Age, Customized <40 years | 1 Participants |
| Age, Customized 50-59 years | 9 Participants |
| Age, Customized 60-69 years | 17 Participants |
| Age, Customized >= 70 years | 22 Participants |
| Nasogastric tube (NGT) Status at Baseline With NGT at baseline | 35 Participants |
| Nasogastric tube (NGT) Status at Baseline Without NGT at baseline | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 51 Participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 52 |
| other Total, other adverse events | 38 / 52 |
| serious Total, serious adverse events | 29 / 52 |
Outcome results
Primary
Percentage of Responders Before or at Day 7
The primary endpoint assessed the percentage of responding subjects before or at Day 7. A responder was defined as a subject experiencing ≤2 vomiting episodes/day during at least 3 consecutive days at any timepoint between Day 0 and Day 7 (for subjects without NGT at baseline), or as a subject in whom the NGT had been removed during at least 3 consecutive days at any timepoint between Day 0 and Day 7 without vomiting recurrence (for subjects with NGT at baseline), as recorded on diary cards which were completed every day.
Time frame: From Day 0 to Day 7
Population: All subjects who received at least 1 dose of study medication (ITT population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Day 7 | Without NGT at Baseline | 88.2 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Day 7 | With NGT at Baseline | 25.7 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Day 7 | All Subjects | 46.2 percentage of responders |
Comparison: One sided binomial test to compare percentage of responding subjects to theoretical proportion of 30%.p-value: 0.0055Binomial test
Secondary
Median Change From Baseline in Abdominal Pain Scores Assessed Using Visual Analogue Scale (VAS) in Phase 1
Abdominal pain was assessed using the VAS numeric pain distress scale. The VAS is a 100-millimetre (10-centimetre) scoring scale on which subjects marked on their perceived level of pain. Score range on VAS is from 0 to 100 where 0 = no pain and 100 = unbearable pain. Median change from baseline (Day 0) at each of the Phase 1 timepoints is presented and a positive change indicates a worsening condition.
Time frame: Days 0, 7, 14 and 28
Population: All subjects who received at least 1 dose of study medication (ITT population). Only subjects with data available for analysis at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Abdominal Pain Scores Assessed Using Visual Analogue Scale (VAS) in Phase 1 | At Day 28 | 0.0 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Abdominal Pain Scores Assessed Using Visual Analogue Scale (VAS) in Phase 1 | At Day 7 | -3.0 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Abdominal Pain Scores Assessed Using Visual Analogue Scale (VAS) in Phase 1 | At Day 14 | -1.0 units on a scale |
Secondary
Median Change From Baseline in General Activity as Assessed by the Karnofsky Performance Status (KPS) Scale in Phase 1
The KPS scale was used to quantify subject's general well-being and activities of daily life. Subjects were classified based on their functional impairment and KPS scores range from 0 (death) to 100 (no evidence of disease). KPS scores are classified as 0-40 = unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly; 50-70 = unable to work; able to live at home and care for most personal needs; varying amount of assistance needed; 80-100 = able to carry on normal activity and to work; no special care needed. Median change from baseline (Day 0) at each of the Phase 1 timepoints is presented and a negative change indicates a worsening condition.
Time frame: Days 0, 7, 14 and 28
Population: All subjects who received at least 1 dose of study medication (ITT population). Only subjects with data available for analysis at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lanreotide Autogel® 120 mg | Median Change From Baseline in General Activity as Assessed by the Karnofsky Performance Status (KPS) Scale in Phase 1 | At Day 7 | 0.0 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in General Activity as Assessed by the Karnofsky Performance Status (KPS) Scale in Phase 1 | At Day 14 | 0.0 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in General Activity as Assessed by the Karnofsky Performance Status (KPS) Scale in Phase 1 | At Day 28 | 10.0 units on a scale |
Secondary
Median Change From Baseline in Number of Daily Episodes of Nausea in Phase 1
The mean number of daily episodes of nausea were calculated as the sum of episodes of nausea reported the last 3 days before the corresponding visit, divided by 3. The median change from baseline (Day 0) at each of the Phase 1 timepoints is presented and positive change indicates a worsening condition.
Time frame: Days 0, 7, 14 and 28
Population: All subjects who received at least 1 dose of study medication (ITT population). Only subjects with data available for analysis at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Number of Daily Episodes of Nausea in Phase 1 | At Day 7 | -0.17 Daily episodes of nausea |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Number of Daily Episodes of Nausea in Phase 1 | At Day 14 | -1.50 Daily episodes of nausea |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Number of Daily Episodes of Nausea in Phase 1 | At Day 28 | -1.50 Daily episodes of nausea |
Secondary
Median Change From Baseline in Quality of Life as Assessed by Edmonton Symptom Assessment System (ESAS) in Phase 1
Quality of Life was assessed by both subject and investigator based on the ESAS. The ESAS scale evaluates 9 symptoms common in cancer subjects: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath. The severity at the time of assessment of each symptom is rated from 0 to 10 on a numerical scale; 0 = symptom is absent and 10 = worst possible severity. Each symptom rating was interpreted independently and a total symptom distress score was calculated for both subject and investigator assessed scores as the sum of the 9 items. Median change from baseline (Day 0) in total symptom distress score, at each of the Phase 1 timepoints is presented and a positive change indicates a worsening condition.
Time frame: Days 0, 7, 14 and 28
Population: All subjects who received at least 1 dose of study medication (ITT population). Only subjects with data available for analysis at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by Edmonton Symptom Assessment System (ESAS) in Phase 1 | Day 28 - assessed by subject | -5.5 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by Edmonton Symptom Assessment System (ESAS) in Phase 1 | Day 7 - assessed by subject | -3.0 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by Edmonton Symptom Assessment System (ESAS) in Phase 1 | Day 7 - assessed by investigator | -4.5 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by Edmonton Symptom Assessment System (ESAS) in Phase 1 | Day 14 - assessed by subject | -2.0 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by Edmonton Symptom Assessment System (ESAS) in Phase 1 | Day 14 - assessed by investigator | -7.5 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by Edmonton Symptom Assessment System (ESAS) in Phase 1 | Day 28 - assessed by investigator | -5.0 units on a scale |
Secondary
Median Change From Baseline in Quality of Life as Assessed by ESAS in Phase 2
Quality of Life was assessed by both subject and investigator based on the ESAS. The ESAS scale evaluates 9 symptoms common in cancer subjects: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath. The severity at the time of assessment of each symptom is rated from 0 to 10 on a numerical scale, 0 = symptom is absent and 10 = worst possible severity. Each symptom rating was interpreted independently and a total symptom distress score was calculated for both subject and investigator assessed scores as the sum of the 9 items. Median change from baseline (Day 0) in total symptom distress score, at each of the Phase 2 timepoints is presented and a positive change indicates a worsening condition.
Time frame: Days 0, 35, 42 and 56
Population: All subjects who received at least 1 dose of study medication (ITT population) and were continuing in Phase 2 of the study. Only subjects with data available for analysis at each timepoint are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by ESAS in Phase 2 | Day 35 - assessed by subject | -4.0 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by ESAS in Phase 2 | Day 35 - assessed by investigator | -12.0 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by ESAS in Phase 2 | Day 42 - assessed by subject | -10.5 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by ESAS in Phase 2 | Day 42 - assessed by investigator | -13.5 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by ESAS in Phase 2 | Day 56 - assessed by subject | -8.0 units on a scale |
| Lanreotide Autogel® 120 mg | Median Change From Baseline in Quality of Life as Assessed by ESAS in Phase 2 | Day 56 - assessed by investigator | -9.0 units on a scale |
Secondary
Median Time Between First Lanreotide Autogel® Injection and Clinical Response in Phase 1
The time for clinical response in Phase 1 (up to Day 28) was defined as the time from inclusion (Day 0) to the date of clinical response. A response was defined as occurrence of ≤ 2 vomiting episodes/day for at least 3 consecutive days at any timepoint between Day 0 and Day 28 (for patients without NGT use at baseline) or the removal of NGT for at least 3 consecutive days at any timepoint between Day 0 and Day 28 without vomiting recurrence (for patients with NGT use at baseline). The Kaplan-Meier estimate of median time to clinical response are presented.
Time frame: From Day 0 to Day 28
Population: All subjects who received at least 1 dose of study medication (ITT population).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanreotide Autogel® 120 mg | Median Time Between First Lanreotide Autogel® Injection and Clinical Response in Phase 1 | 9.00 days |
Secondary
Percentage of Responders Before or at Phase 2 Timepoints
This endpoint assessed the overall percentage of subjects continuing from Phase 1 and confirmed as a responder at the end of Phase 1, showing a continued response at Days 35, 42 and 56. A responder was defined as a subject experiencing ≤2 vomiting episodes/day during at least 3 consecutive days at any timepoint between Day 0 and Days 35, 42, 56 (for subjects without NGT at baseline), or as a subject in whom the NGT had been removed during at least 3 consecutive days at any timepoint between Day 0 and Days 35, 42, 56 without vomiting recurrence (for subjects with NGT at baseline), as recorded on diary cards which were completed every day.
Time frame: From Day 0 to Day 56
Population: All subjects who received at least 1 dose of study medication (ITT population) and were continuing in Phase 2 of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Phase 2 Timepoints | By Day 35: Without NGT at Baseline | 100 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Phase 2 Timepoints | By Day 35: With NGT at Baseline | 100 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Phase 2 Timepoints | By Day 35: All Subjects | 100 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Phase 2 Timepoints | By Day 42: Without NGT at Baseline | 100 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Phase 2 Timepoints | By Day 42: With NGT at Baseline | 100 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Phase 2 Timepoints | By Day 42: All Subjects | 100 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Phase 2 Timepoints | By Day 56: Without NGT at Baseline | 100 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Phase 2 Timepoints | By Day 56: With NGT at Baseline | 100 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders Before or at Phase 2 Timepoints | By Day 56: All Subjects (n=21) | 100 percentage of responders |
Secondary
Percentage of Responders in Phase 1
This endpoint assessed the overall percentage of responding subjects at the Phase 1 timepoints of Days 14 and 28. A responder was defined as a subject experiencing ≤ 2 vomiting episodes/day during at least 3 consecutive days at any timepoint between Day 0 and Days 14 or 28 (for subjects without NGT at baseline) or as a subject in whom the NGT has been removed, during at least 3 consecutive days without vomiting recurrence, at any timepoint between Day 0 and Days 14 and 28 (for subjects with NGT at baseline), as recorded on diary cards which were completed every day.
Time frame: From Day 0 to Day 28
Population: All subjects who received at least 1 dose of study medication (ITT population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanreotide Autogel® 120 mg | Percentage of Responders in Phase 1 | By Day 28: All Subjects | 65.4 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders in Phase 1 | By Day 14: Without NGT at Baseline | 88.2 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders in Phase 1 | By Day 14: With NGT at Baseline | 45.7 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders in Phase 1 | By Day 14: All Subjects | 59.6 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders in Phase 1 | By Day 28: Without NGT at Baseline | 88.2 percentage of responders |
| Lanreotide Autogel® 120 mg | Percentage of Responders in Phase 1 | By Day 28: With NGT at Baseline | 54.3 percentage of responders |