Non Functioning Entero-pancreatic Endocrine Tumour
Conditions
Keywords
Lanreotide, Somatuline, Neuroendocrine tumour, NET
Brief summary
The primary purpose of this extension study was to assess the long term safety of patients with nonfunctioning enteropancreatic neuroendocrine tumour (NET), who were treated with open label lanreotide Autogel (120 mg every 28 days) and who participated in a previous study, 2-55-52030-726 (NCT00353496).
Detailed description
While somatostatin analogue treatment is the primary medical therapy for patients with hormone related symptoms and is indicated for the treatment of hormone related symptoms in many international countries, there is no reference standard medical therapy for asymptomatic patients. A 96-week study (Study 2-55-52030-726 (726), NCT00353496) was conducted to investigate the effect of lanreotide Autogel on progression free survival (PFS) in patients with well or moderately differentiated nonfunctioning enteropancreatic NET. While Study 726 was ongoing, the sponsor considered that therapy with lanreotide Autogel should continue to be an option to patients with stable disease at the end of the 96-week treatment period. This extension study was therefore initiated (Study 2-55-52030-729 (729)) which investigated the long term safety of treatment with lanreotide Autogel and enabled investigators to continue to treat their patients who had stable disease, as well as to treat placebo patients who experienced disease progression during the initial 96-week study (Study 726).
Interventions
Autogel 120 mg
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Had provided written informed consent prior to any study-related procedures. 2. Had been enrolled and treated in Study 2-55-52030-726 and either: * Was stable at 96 weeks of treatment (whatever the treatment received during the 2 years of participation, i.e. no code break at Week 96); or, * Had received at least one injection in Study 2-55-52030-726 and had disease progression, confirmed by central assessment, during the course of the study and code break showed placebo. 3. Had a World Health Organisation (WHO) performance score lower than or equal to 2.
Exclusion criteria
1. Had been enrolled and treated in the frame of the protocol and had disease progression during the study and the code break showed a treatment with lanreotide Autogel 120 mg. 2. Had received any new treatment for the entero-pancreatic NET since the end of participation in the study. 3. Were likely to require any additional concomitant treatment to lanreotide Autogel 120 mg for the entero-pancreatic NET. 4. Had been treated with radionuclide at any time prior to study entry. 5. Had a history of hypersensitivity to drugs with a similar chemical structure to lanreotide Autogel 120 mg. 6. Were likely to require treatment during the study with drugs that were not permitted by the study protocol. 7. Were at risk of pregnancy or lactation. Females of childbearing potential had to provide a negative pregnancy test at the start of study and had to be using oral, double barrier or injectable contraception. Non-childbearing potential was defined as postmenopause for at least 1 year, or surgical sterilisation or hysterectomy at least 3 months before the start of the study. 8. Had any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude. 9. Had abnormal findings at Visit 1, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might have jeopardised the patient's safety or decreased the chance of obtaining satisfactory data needed to achieve the objective(s) of the study. 10. Previous enrolment in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Throughout the study until the completion/early discontinuation visit. | Adverse events (AEs) that were ongoing from Study 726 at the time of entry into Study 729 were transcribed into the case report form (CRF) for Study 729 with a start date corresponding to the original report of this AE in Study 726. All new AEs that started after the last visit in Study 726 (i.e. irrespective of whether the AE had onset before or after giving informed consent for Study 729) were recorded Study 729. An AE was considered as a treatment emergent adverse event (TEAE) for Study 729 if: * It was not present prior to receiving the first dose of study treatment in Study 729; or, * It was present prior to receiving the first dose of study treatment in Study 729 but the intensity increased after the first dose of study treatment in Study 729. Adverse event data are presented in the AE section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS): Kaplan-Meier Estimate | Throughout the study (every 24 weeks and at completion/withdrawal visit) | The time from randomisation in Study 726 to the first occurrence of either disease progression (measured using Response Evaluation Criteria In Solid Tumours \[RECIST\] criteria) or death in Study 726 or in Study 729, or equivalently, the Progression Free Survival (PFS) time. Tumour assessments for the placebo group after switching to open label lanreotide Autogel were excluded for the purpose of this analysis. Estimation of the median was based on the Kaplan-Meier method. |
Countries
Belgium, Czechia, France, Italy, Poland, Slovakia, Spain, United Kingdom, United States
Participant flow
Recruitment details
There were 26 active sites across 10 countries in Study 729; however, only 24 recruited patients. The study was initiated in February 2009 and was completed in December 2015.
Participants by arm
| Arm | Count |
|---|---|
| Lanreotide Autogel Patients who received lanreotide 120 mg (Autogel formulation) in the preceding DB study (Study 2-55-52030-726) and who continued to receive lanreotide 120 mg (Autogel formulation) in the open label study. | 42 |
| Placebo Patients who received placebo in the preceding DB study (Study 2-55-52030-726) and who received lanreotide 120 mg (Autogel formulation) in the open label study. | 47 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Patients Randomised in Study 726 | Did not enter Study 729 | 59 | 56 |
| Study 729 | Adverse Event | 1 | 1 |
| Study 729 | Disease progression/death | 19 | 30 |
| Study 729 | Due to non-availability of IP | 0 | 1 |
| Study 729 | Due to Sponsor stopping the study | 1 | 1 |
| Study 729 | Protocol Violation | 1 | 1 |
| Study 729 | Sponsor's decision | 1 | 0 |
| Study 729 | Surgical resection | 1 | 0 |
| Study 729 | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Lanreotide Autogel | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 10.8 | 61.3 years STANDARD_DEVIATION 10.2 | 62.9 years STANDARD_DEVIATION 10.6 |
| Race/Ethnicity, Customized Asian | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian/White | 41 participants | 44 participants | 85 participants |
| Sex: Female, Male Female | 23 Participants | 22 Participants | 45 Participants |
| Sex: Female, Male Male | 19 Participants | 25 Participants | 44 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 | 34 / 42 | 42 / 47 | 76 / 89 |
| serious Total, serious adverse events | 11 / 42 | 14 / 47 | 25 / 89 |
Outcome results
Primary
Adverse Events
Adverse events (AEs) that were ongoing from Study 726 at the time of entry into Study 729 were transcribed into the case report form (CRF) for Study 729 with a start date corresponding to the original report of this AE in Study 726. All new AEs that started after the last visit in Study 726 (i.e. irrespective of whether the AE had onset before or after giving informed consent for Study 729) were recorded Study 729. An AE was considered as a treatment emergent adverse event (TEAE) for Study 729 if: * It was not present prior to receiving the first dose of study treatment in Study 729; or, * It was present prior to receiving the first dose of study treatment in Study 729 but the intensity increased after the first dose of study treatment in Study 729. Adverse event data are presented in the AE section.
Time frame: Throughout the study until the completion/early discontinuation visit.
Population: Safety population: all patients who received at least one dose of lanreotide Autogel in Study 729.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanreotide Autogel | Adverse Events | 40 participants with any TEAEs |
| Placebo | Adverse Events | 46 participants with any TEAEs |
| Total | Adverse Events | 86 participants with any TEAEs |
Secondary
Progression Free Survival (PFS): Kaplan-Meier Estimate
The time from randomisation in Study 726 to the first occurrence of either disease progression (measured using Response Evaluation Criteria In Solid Tumours \[RECIST\] criteria) or death in Study 726 or in Study 729, or equivalently, the Progression Free Survival (PFS) time. Tumour assessments for the placebo group after switching to open label lanreotide Autogel were excluded for the purpose of this analysis. Estimation of the median was based on the Kaplan-Meier method.
Time frame: Throughout the study (every 24 weeks and at completion/withdrawal visit)
Population: Intention-to-treat (ITT) population: all patients randomised in the original protocol Study 726 (regardless of whether they continued into the extension Study 729). The ITT population was analysed using patients as randomised in Study 726.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanreotide Autogel | Progression Free Survival (PFS): Kaplan-Meier Estimate | 154.14 weeks |
| Placebo | Progression Free Survival (PFS): Kaplan-Meier Estimate | 72.00 weeks |