Neuroendocrine Tumour With Carcinoid Symptoms
Conditions
Brief summary
The primary aim of this study is to assess which method of lanreotide Autogel administration patients with neuroendocrine tumours prefer - self/partner administrations or healthcare provided administrations. The study will also assess if self/partner administration can be performed without loss of efficacy and with a preserved safety profile. The impact of self/partner administration on resource utilisation and costs will be studied. In addition, we will also assess the healthcare provider's experience of the two administration practices.
Interventions
90 mg or 120 mg once every 28th day
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent from the patient and their partner (if the partner will be administering the lanreotide Autogel injections during the self administration period) * Male or female aged 18 years of age or older * Treated with lanreotide Autogel 90 or 120 mg every 28th day for carcinoid symptoms on a stable dose for at least 3 months prior to inclusion. The patient is presumed to be clinically stable during the coming months * Neuroendocrine tumour confirmed by biopsy and visible on radiology
Exclusion criteria
* Has a history of hypersensitivity to the Investigational Medicinal Product or drugs with a similar chemical structure * Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study * Has a life expectancy less than a year, as judged by the Investigator * The patient or their partner is not considered competent in injection technique, as judged by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject Preference for Self or Partner Administration | Between week 30 to 34 | A global question was asked: 'If you could choose, which administration method would you like to use on a regular basis?' A) Healthcare professional provided injection B) Self/ partner administered injection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Stating at Least One Injection Negatively Interfered With Psychological Wellbeing | Between baseline to week 32, after each injection (8-9 injections) | The subject was asked: 'Does the treatment administration used today negatively interfere with your psychological wellbeing?' |
| Days Sick Leave | Group 1 - between week 8 to 20 (self or partner administration), between week 20 to 32 (HCP administration). Group 2 - between week 20 to 32 (self or partner administration), between week 0 to week 12 (HCP administration) | Health care and patient costs associated with the treatment of carcinoid symptoms in subjects treated with lanreotide Autogel were assessed through recording loss of production for subject through total number of days sick leave of the employed patients (n=6). |
| Total Number of Visits to HCP Due to Carcinoid Symptoms | Group 1 - between week 8 to 20 (self or partner administration), between week 20 to 32 (HCP administration). Group 2 - between week 20 to 32 (self or partner administration), between week 0 to week 12 (HCP administration) | Health care and patient costs associated with the treatment of carcinoid symptoms in subjects treated with lanreotide Autogel were assessed by recording the total number of visits made by participants (n=12) to HCP due to carcinoid symptoms. |
| Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Group 1 - baseline, week 16 to 20 (self or partner administration) and week 30 to 34 (HCP administration). Group 2 - baseline, week 12 (HCP administration) and week 30 (self or partner administration). | Participants were asked how they perceived the symptoms in respect to episodes of flushing since the last injection. Participants included in the study were previously treated with lanreotide Autogel and therefore the assessment at baseline was made in comparison to their previous injection outside of the study protocol. |
| Number of Patients Stating at Least One Injection Interfered With Daily Activities | Between baseline to week 32, after each injection (8-9 injections) | The subject was asked: 'Does the treatment administration used today interfere with your daily activities?' |
| Chromogranin A Levels | Group 1 - Baseline, week 16 to 20 and 30 to 34. Group 2 - Baseline, week 12 and 30 to 34. | Biochemical control was assessed by analysing chromogranin A levels at each site visit, which was mandatory for all subjects. 'Before self or partner administration' was assessed at baseline for group 1 and at week 12 for group 2. 'After self or partner administration' was assessed at week 16 to 20 for group 1 and at week 12 for group 2. 'Before HCP administration' was assessed at week 16 to 20 for group 1 and at baseline for group 2. 'After HCP administration' was assessed at week 30 to 34 for group 1 and week 12 for group 2. |
| 5-hydroxyindoleacetic Acid (5-HIAA) Levels | Group 1 - Baseline, week 16 to 20 and 30 to 34. Group 2 - Baseline, week 12 and 30 to 34. | Biochemical control was assessed by analysing 5-HIAA levels at each site visit, which was judged as necessary by the investigator at each site. 'Before self or partner administration' was assessed at baseline for group 1 and at week 12 for group 2. 'After self or partner administration' was assessed at week 16 to 20 for group 1 and at week 12 for group 2. 'Before HCP administration' was assessed at week 16 to 20 for group 1 and at baseline for group 2. 'After HCP administration' was assessed at week 30 to 34 for group 1 and week 12 for group 2. |
| Healthcare Professionals With Positive Response to Specified Questions on Self or Partner Administration Method | Between week 30 to 34 | Assessed by the number of HCP with a positive response 'yes' to two questions: 1. Based on your experience during this trial, did you feel confident in the safety of your patients? 2. Based on your experience during this trial, would you recommend suitable patients to try self or partner administration? |
| Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Group 1 - baseline, week 16 to 20 (self or partner administration) and week 30 to 34 (HCP administration). Group 2 - baseline, week 12 to 16 (HCP administration) and week 30 to 34 (self or partner administration). | Participants were asked how they perceived the symptoms in respect to episodes of diarrhoea since the last injection. Participants included in the study were previously treated with lanreotide autogel and therefore the assessment at baseline was made in comparison to previous injection outside of the study protocol. |
Countries
Denmark, Norway, Sweden
Participant flow
Recruitment details
Data from ninety-four subjects was reviewed in hospital clinics in Denmark, Norway and Sweden. Of which 32 were ineligible, 36 were eligible but chose not to participate due to lack of motivation, satisfaction with current form of administration or fear of self-injection and 26 were included. Patients were recruited from Jun-08 to Jan-10.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Self or Partner First Then HCP Administration Self or partner administration followed by HCP administration. | 11 |
| Group 2 HCP Then Self or Partner Administration Administration by HCP then self or partner administration. | 15 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Group 2 HCP Then Self or Partner Administration | Total | Group 1 Self or Partner First Then HCP Administration |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 12 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 14 Participants | 6 Participants |
| Age, Continuous | 60.0 years STANDARD_DEVIATION 12.7 | 61.4 years STANDARD_DEVIATION 10.5 | 63.2 years STANDARD_DEVIATION 6.5 |
| Region of Enrollment Denmark | 4 participants | 7 participants | 3 participants |
| Region of Enrollment Norway | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Sweden | 8 participants | 15 participants | 7 participants |
| Sex: Female, Male Female | 8 Participants | 12 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 26 | 4 / 26 | 7 / 26 |
| serious Total, serious adverse events | 4 / 26 | 4 / 26 | 3 / 26 |
Outcome results
Primary
Subject Preference for Self or Partner Administration
A global question was asked: 'If you could choose, which administration method would you like to use on a regular basis?' A) Healthcare professional provided injection B) Self/ partner administered injection
Time frame: Between week 30 to 34
Population: Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | Subject Preference for Self or Partner Administration | 10 participants |
| Group 2 HCP Then Self or Partner Administration | Subject Preference for Self or Partner Administration | 12 participants |
Secondary
5-hydroxyindoleacetic Acid (5-HIAA) Levels
Biochemical control was assessed by analysing 5-HIAA levels at each site visit, which was judged as necessary by the investigator at each site. 'Before self or partner administration' was assessed at baseline for group 1 and at week 12 for group 2. 'After self or partner administration' was assessed at week 16 to 20 for group 1 and at week 12 for group 2. 'Before HCP administration' was assessed at week 16 to 20 for group 1 and at baseline for group 2. 'After HCP administration' was assessed at week 30 to 34 for group 1 and week 12 for group 2.
Time frame: Group 1 - Baseline, week 16 to 20 and 30 to 34. Group 2 - Baseline, week 12 and 30 to 34.
Population: 5-HIAA were assessed as judged necessary by the investigator at each site.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | 5-hydroxyindoleacetic Acid (5-HIAA) Levels | 220.17 nmol/l | Standard Deviation 238.32 |
| Group 2 HCP Then Self or Partner Administration | 5-hydroxyindoleacetic Acid (5-HIAA) Levels | 219.17 nmol/l | Standard Deviation 227.64 |
| HCP Administration | 5-hydroxyindoleacetic Acid (5-HIAA) Levels | 217.08 nmol/l | Standard Deviation 244.32 |
| After HCP Administration | 5-hydroxyindoleacetic Acid (5-HIAA) Levels | 219.58 nmol/l | Standard Deviation 218.51 |
Secondary
Chromogranin A Levels
Biochemical control was assessed by analysing chromogranin A levels at each site visit, which was mandatory for all subjects. 'Before self or partner administration' was assessed at baseline for group 1 and at week 12 for group 2. 'After self or partner administration' was assessed at week 16 to 20 for group 1 and at week 12 for group 2. 'Before HCP administration' was assessed at week 16 to 20 for group 1 and at baseline for group 2. 'After HCP administration' was assessed at week 30 to 34 for group 1 and week 12 for group 2.
Time frame: Group 1 - Baseline, week 16 to 20 and 30 to 34. Group 2 - Baseline, week 12 and 30 to 34.
Population: ITT population that had hormone levels assessed at each administration block.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | Chromogranin A Levels | 37.48 nmol/l | Standard Deviation 58.35 |
| Group 2 HCP Then Self or Partner Administration | Chromogranin A Levels | 47.85 nmol/l | Standard Deviation 74.89 |
| HCP Administration | Chromogranin A Levels | 42.05 nmol/l | Standard Deviation 70.74 |
| After HCP Administration | Chromogranin A Levels | 37.42 nmol/l | Standard Deviation 57.96 |
Secondary
Days Sick Leave
Health care and patient costs associated with the treatment of carcinoid symptoms in subjects treated with lanreotide Autogel were assessed through recording loss of production for subject through total number of days sick leave of the employed patients (n=6).
Time frame: Group 1 - between week 8 to 20 (self or partner administration), between week 20 to 32 (HCP administration). Group 2 - between week 20 to 32 (self or partner administration), between week 0 to week 12 (HCP administration)
Population: Safety population: all randomised subjects with at least one dose of study medication. Two of the six subjects reported sick leave during the study. One subject was absent for one day due to unknown reason, the other was absent for 22 days due to surgery of metastasis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | Days Sick Leave | 23 days |
| Group 2 HCP Then Self or Partner Administration | Days Sick Leave | 0 days |
Secondary
Healthcare Professionals With Positive Response to Specified Questions on Self or Partner Administration Method
Assessed by the number of HCP with a positive response 'yes' to two questions: 1. Based on your experience during this trial, did you feel confident in the safety of your patients? 2. Based on your experience during this trial, would you recommend suitable patients to try self or partner administration?
Time frame: Between week 30 to 34
Population: One HCP from each site who enrolled participants replied to the question
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | Healthcare Professionals With Positive Response to Specified Questions on Self or Partner Administration Method | 9 participants |
Secondary
Number of Patients Stating at Least One Injection Interfered With Daily Activities
The subject was asked: 'Does the treatment administration used today interfere with your daily activities?'
Time frame: Between baseline to week 32, after each injection (8-9 injections)
Population: Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | Number of Patients Stating at Least One Injection Interfered With Daily Activities | 6 Participants |
| Group 2 HCP Then Self or Partner Administration | Number of Patients Stating at Least One Injection Interfered With Daily Activities | 2 Participants |
| HCP Administration | Number of Patients Stating at Least One Injection Interfered With Daily Activities | 6 Participants |
Secondary
Number of Patients Stating at Least One Injection Negatively Interfered With Psychological Wellbeing
The subject was asked: 'Does the treatment administration used today negatively interfere with your psychological wellbeing?'
Time frame: Between baseline to week 32, after each injection (8-9 injections)
Population: Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | Number of Patients Stating at Least One Injection Negatively Interfered With Psychological Wellbeing | 4 participants |
| Group 2 HCP Then Self or Partner Administration | Number of Patients Stating at Least One Injection Negatively Interfered With Psychological Wellbeing | 2 participants |
| HCP Administration | Number of Patients Stating at Least One Injection Negatively Interfered With Psychological Wellbeing | 1 participants |
Secondary
Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea
Participants were asked how they perceived the symptoms in respect to episodes of diarrhoea since the last injection. Participants included in the study were previously treated with lanreotide autogel and therefore the assessment at baseline was made in comparison to previous injection outside of the study protocol.
Time frame: Group 1 - baseline, week 16 to 20 (self or partner administration) and week 30 to 34 (HCP administration). Group 2 - baseline, week 12 to 16 (HCP administration) and week 30 to 34 (self or partner administration).
Population: Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Improved | 2 participants |
| Group 1 Self or Partner First Then HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Missing | 0 participants |
| Group 1 Self or Partner First Then HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Similar | 22 participants |
| Group 1 Self or Partner First Then HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Worsened | 1 participants |
| Group 2 HCP Then Self or Partner Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Worsened | 4 participants |
| Group 2 HCP Then Self or Partner Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Similar | 17 participants |
| Group 2 HCP Then Self or Partner Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Missing | 1 participants |
| Group 2 HCP Then Self or Partner Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Improved | 3 participants |
| HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Missing | 0 participants |
| HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Worsened | 0 participants |
| HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Similar | 24 participants |
| HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea | Improved | 1 participants |
Secondary
Perceived Symptom Control Evaluation in Respect to Episodes of Flushing
Participants were asked how they perceived the symptoms in respect to episodes of flushing since the last injection. Participants included in the study were previously treated with lanreotide Autogel and therefore the assessment at baseline was made in comparison to their previous injection outside of the study protocol.
Time frame: Group 1 - baseline, week 16 to 20 (self or partner administration) and week 30 to 34 (HCP administration). Group 2 - baseline, week 12 (HCP administration) and week 30 (self or partner administration).
Population: Analysis was performed on Intention to Treat population defined as all randomised subjects with ≥ 1 dose of study medication and with a preference assessment recorded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Worsened | 0 participants |
| Group 1 Self or Partner First Then HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Similar | 24 participants |
| Group 1 Self or Partner First Then HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Improved | 1 participants |
| Group 1 Self or Partner First Then HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Missing | 0 participants |
| Group 2 HCP Then Self or Partner Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Missing | 1 participants |
| Group 2 HCP Then Self or Partner Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Worsened | 1 participants |
| Group 2 HCP Then Self or Partner Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Improved | 2 participants |
| Group 2 HCP Then Self or Partner Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Similar | 21 participants |
| HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Missing | 0 participants |
| HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Similar | 20 participants |
| HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Improved | 4 participants |
| HCP Administration | Perceived Symptom Control Evaluation in Respect to Episodes of Flushing | Worsened | 1 participants |
Secondary
Total Number of Visits to HCP Due to Carcinoid Symptoms
Health care and patient costs associated with the treatment of carcinoid symptoms in subjects treated with lanreotide Autogel were assessed by recording the total number of visits made by participants (n=12) to HCP due to carcinoid symptoms.
Time frame: Group 1 - between week 8 to 20 (self or partner administration), between week 20 to 32 (HCP administration). Group 2 - between week 20 to 32 (self or partner administration), between week 0 to week 12 (HCP administration)
Population: Safety population: all randomised subjects with at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 Self or Partner First Then HCP Administration | Total Number of Visits to HCP Due to Carcinoid Symptoms | 17 visits |
| Group 2 HCP Then Self or Partner Administration | Total Number of Visits to HCP Due to Carcinoid Symptoms | 25 visits |