Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Lanreotide

Somatostatin

Hormones

Hormone Antagonists

120mg every 28 days until disease progression, death, or unacceptable toxicity

120mg every 28 days until disease progression, death, or unacceptable toxicity during the double-blind phase. The patient may enter open-label phase for treatment with Lanreotide.

Lanreotide (Autogel formulation)

Saline solution 0.9% administered via deep subcutaneous injection every 28 days until disease progression.

Placebo

Best Supportive Care is best available therapy at the choice of the investigator

Best Supportive Care

Ipsen Medical Director

This is a Phase 3, prospective, multi-center, randomized, double-blind, study evaluating the efficacy and safety of LAN plus BSC versus placebo plus BSC for the treatment of well-differentiated, metastatic and/or unresectable, typical or atypical bronchopulmonary NETs.

This study contains two phases: the Double-Blind (DB) Phase, and the Open Label (OL) Phase. The DB Phase includes: Screening, Baseline and Treatment period. The OL Phase will consist of two periods: Treatment Period and Follow-Up Period.

The primary objective will be to describe the antitumour efficacy of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) every 28 days, in terms of progression-free survival (PFS), measured by central review using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria, every 12 weeks, in subjects randomized to LAN with unresectable and/or metastatic well differentiated, typical or atypical bronchopulmonary neuroendocrine tumours.

Recent updates of National Cancer Institute Cancer Network (NCCN) \& European Neuroendocrine Tumor Society (ENETS) guidelines recommend SSA in first line for the treatment of locoregional unresectable or metastatic bronchopulmonary NETs as an option beyond 'observation' leading to slow and difficult recruitment in SPINET study. Consequently, it was decided to prematurely stop the recruitment in the SPINET study and to transition all subjects still treated in the double-blind phase to the open label (OL) treatment and follow-up phases following respective country approvals of Amendment #5.

The new aim of this Phase 3, multicenter, prospective, randomized placebo-controlled clinical study is to describe the antitumor efficacy and safety of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) in subjects with well-differentiated, metastatic and/or unresectable, typical or atypical, bronchopulmonary NETs.

As planned initially, a total of 216 eligible patients with well-differentiated typical or atypical, metastatic and/or unresectable bronchopulmonary NETs, and a positive somatostatin receptor imaging (SRI) (Octreoscan® ≥ grade 2 Krenning scale; Ga-PET scan: uptake greater than liver background), were to be randomized 2:1 to either LAN plus BSC (120mg/28 days) or placebo plus BSC following the stratification of 1) typical versus atypical and 2) prior chemotherapy versus no prior chemotherapy\*.

\* cytotoxic chemotherapy or molecular targeted therapy or interferon.

At the time of the premature stop of the recruitment (as per Protocol Amendment #5), 77 patients were enrolled. All patients still treated in the DB Phase were entered into the OL Phase (either for Follow up or for OL treatment periods). The transition to the OL periods was done on a country-basis and per patient, at the following planned scheduled visit (i.e. approximately 28 days from the last injection). Patients enrolled into the study not progressing at the time of study stop, and who agree to stay on LAN therapy (i.e. OL Treatment Period) receive the study active treatment until evidence of disease progression (based on local radiological assessment then confirmed centrally), development of unacceptable toxicity, or premature withdrawal for any reason or up a maximum of 18 months after the last patient randomized. After disease progression patients are followed for survival, QoL and all subsequent anticancer treatments in the OL Follow-up period up to the end of the study (i.e up to 18 months after the last patient randomized).

Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumours

A Phase 3, Prospective, Randomized, Double-blind, Multi-center Study of the Efficacy and Safety of Lanreotide Autogel®/Depot 120 mg Plus BSC vs. Placebo Plus BSC for Tumour Control in Subjects With Well Differentiated, Metastatic and/or Unresectable, Typical or Atypical, Lung Neuroendocrine Tumours

PFS for subjects randomised in the lanreotide group, assessed by central review using Response Evaluation Criteria In Solid Tumours Version 1.1 (RECIST v1.1) criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during either the double-blind phase, or the open-label treatment phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

PFS was assessed by central review using RECIST v1.1 criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during the double-blind phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

PFS was assessed by local review using RECIST v1.1 criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during the double-blind phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

ORR was assessed by central review and local review using RECIST v1.1 criteria every 12 weeks, defined as the percentage of subjects who achieved a best overall response of complete response or partial response in the double-blind phase.

TTF was defined as the time from randomisation to disease progression using RECIST v1.1, death, consent withdrawn, an adverse event, protocol deviations, lost to follow-up, the appearance of carcinoid syndrome or other hormone related syndrome necessitating the initiation of SSAs (rescue octreotide and/or long-acting release SSA), or initiation of anticancer treatment in the double-blind phase. The distribution of TTF times were estimated using the Kaplan-Meier product limit method.

Blood samples were collected to determine plasma CgA. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide). The x of upper limit of normal (ULN) was calculated as raw value/ULN.

Measured in subjects with an elevated CgA at baseline (≥2 x ULN). Blood samples were collected to determine plasma CgA. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide).

The EORTC QLQ-C30 (V3.0) consisted of 30 questions. The final 2 questions were related to global health status/QoL, with responses requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The global health status/QoL scale ranges in score from 0 to 100. A high score for the global health status/QoL scale represents a high QoL, thus, an increase in score represents an increase in QoL. 95% Clopper-Pearson confidence intervals were estimated using the exact method for binomial distributions. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide).

QoL deterioration was defined by a decrease from baseline in EORTC QLQ-C30 Global Health Status/QoL Score of at least 10 points. The EORTC QLQ-C30 (V3.0) consisted of 30 questions. The final 2 questions were related to global health status/QoL, with responses requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The global health status/QoL scale ranges in score from 0 to 100. A high score for the global health status/QoL scale represents a high QoL, thus, an increase in score represents an increase in QoL. 95% Clopper-Pearson confidence intervals were estimated using the exact method for binomial distributions. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide).

Measured in subjects with an elevated 5-HIAA at baseline (≥2 x ULN). The assessment of urinary 5-HIAA required subjects to collect their urine for the 24 hour period prior to the study visit. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide). The x of ULN was calculated as raw value/ULN.

Ipsen

The safety population included all subjects who received at least one injection of study treatment. Subjects were analysed as treated.

Subjects received deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and continue to receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. If a subject progressed during the double-blind phase they entered the open-label follow-up phase.

Double-Blind Phase: Lanreotide

Subjects received deep SC injections of placebo (saline solution 0.9%) Q4 weeks plus BSC in the double-blind phase. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC.

Double-Blind Phase: Placebo

Subjects received deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. If a subject progressed during the open-label treatment phase they entered the open-label follow-up phase.

Open-Label Treatment Phase

If the subject received lanreotide autogel/depot and progressed during the double-blind phase or open-label treatment phase, the subject entered the follow-up phase of the open-label treatment phase and was followed for QoL/survival and all subsequent anticancer treatments received. No intervention was received in the open-label follow-up phase.

Open-Label Follow-Up Phase

Subjects received deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. If a subject progressed during the double-blind phase or open-label treatment phase they entered the open-label follow-up phase. The follow-up phase ended at the same time as the open-label treatment phase (18 months after the last subject randomised).

Subjects received deep SC injections of placebo (saline solution 0.9%) Q4 weeks plus BSC in the double-blind phase. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. If a subject progressed during the open-label treatment phase they entered the open-label follow-up phase. The follow-up phase ended at the same time as the open-label treatment phase (18 months after the last subject randomised).

Total

Age, Continuous

Sex: Female, Male

Ethnicity

Race/Ethnicity, Customized

Race

The intention to treat (ITT) population included all randomised subjects. Subjects were analysed as randomised, regardless of the treatment received.

The majority of subjects who entered the open-label treatment phase were withdrawn due to study termination by the sponsor.

Medical Director

Subjects received deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and continue to receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. If a subject progressed during the double-blind phase or open-label treatment phase they entered the open-label follow-up phase. The follow-up phase ended at the same time as the open-label treatment phase (18 months after the last subject randomised).

Overall Study: Lanreotide

The ITT population included all randomised subjects. Subjects were analysed as randomised, regardless of the treatment received. One subject randomised to lanreotide should have been censored in the PFS analysis treatment for discontinuation for toxicity or other reasons, however the baseline central radiological assessment was performed prior to the randomisation date, therefore the subject was excluded from the analysis.

Median Progression-Free Survival (PFS) Time in Subjects Randomised to Lanreotide in the Double-Blind Phase or Open-Label Treatment Phase, Assessed by Central Review

The hazard ratio and the 95% confidence interval (CI) were estimated using a Cox proportional hazards model, stratified for interactive web response system (IWRS) tumour subtype (typical versus \[vs\] atypical) using the exact method for ties. P-value of stratified log rank test comparing lanreotide to placebo with strata based on the IWRS tumour subtype (typical vs atypical) stratification factor.

The ITT population included all randomised subjects. Subjects were analysed as randomised, regardless of the treatment received. One subject in the double-blind phase: lanreotide arm should have been censored in the PFS analysis for treatment discontinuation for toxicity or other reasons, however the baseline central radiological assessment was performed prior to the randomisation date, therefore the subject was excluded from the analysis.

Median PFS Time in the Double-Blind Phase, Assessed by Central Review

The hazard ratio and the 95% CI were estimated using a Cox proportional hazards model, stratified for IWRS tumour subtype (typical vs atypical) using the exact method for ties. P-value of stratified log rank test comparing lanreotide to placebo with strata based on the IWRS tumour subtype (typical vs atypical) stratification factor.

The ITT population included all randomised subjects. Subjects were analysed as randomised, regardless of the treatment received. Two subjects should have been censored in the PFS analysis, however the baseline central radiological assessment was performed prior to the randomisation date, therefore the subjects were excluded from the analysis.

Median PFS Time in the Double-Blind Phase, Assessed by Local Review

The treatment difference compares lanreotide to placebo (central review). The 95% exact unconditional CI was used for ORR difference.

The treatment difference compares lanreotide to placebo (local review). The 95% exact unconditional CI was used for ORR difference.

Central review

Local review

The ITT population included all randomised subjects. Subjects were analysed as randomised, regardless of the treatment received. Two subjects were excluded from the analysis as they had no best response recorded in the raw data.

Objective Response Rate (ORR) in the Double-Blind Phase

The ITT population included all randomised subjects. Subjects were analysed as randomised, regardless of the treatment received.

Time to Treatment Failure (TTF) in the Double-Blind Phase

Week 8

Week 12

Week 24

Week 48

Post-treatment

Open-Label Treatment Phase: All Subjects

Double-blind phase: The ITT population included all randomised subjects with non-missing measurements. Subjects were analysed as randomised, regardless of the treatment received. Open-label phase: The open-label ITT population included all ITT subjects with non-missing measurements entering the open-label phase who received at least one injection of lanreotide autogel/depot in the open-label phase.

Mean Change From Baseline in the Biomarker Chromogranin A (CgA) in the Double-Blind Phase and Open-Label Treatment Phase

Double-blind phase: The ITT population included all randomised subjects with non-missing measurements and elevated CgA at Baseline. Subjects were analysed as randomised, regardless of the treatment received. Open-label phase: The open-label ITT population included all ITT subjects with non-missing measurements and elevated CgA at Baseline entering the open-label phase who received at least one injection of lanreotide autogel/depot in the open-label phase.

Percentage of Subjects With a Decrease of CgA ≥30% From Baseline at Week 8 in the Double-Blind Phase and Open-Label Treatment Phase

Mean Changes From Baseline in Quality of Life (QoL), as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Global Health Status/QoL Score

Percentage of Subjects Who Experienced QoL Deterioration

Double-blind phase: The ITT population included all randomised subjects with non-missing measurements and elevated 5-HIAA at baseline. Subjects were analysed as randomised, regardless of the treatment received. Open-label phase: The open-label ITT population included all ITT subjects with non-missing measurements and elevated 5-HIAA at baseline entering the open-label phase who received at least one injection of lanreotide autogel/depot in the open-label phase.

Mean Changes From Baseline in Urinary 5-hydroxyindoleacetic Acid (5-HIAA) Levels in the Double-Blind Phase and Open-Label Treatment Phase

Subjects received deep subcutaneous (SC) injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and continue to receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. If a subject progressed during the double-blind phase or open-label treatment phase they entered the open-label follow-up phase. The follow-up phase ended at the same time as the open-label treatment phase (18 months after the last subject randomised).

Double-blind Phase

Open-label Treatment Phase

Open-label Follow-up Phase

Carcinoid Tumor

Oculocerebral Syndrome With Hypopigmentation

lanreotide (Autogel formulation)

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.

Somatuline Autogel Preference and Health Economy Study

A Phase IV, International, Open-label, Randomised, Cross-over Study to Assess Patient Preference and Health Economy in Patients With Neuroendocrine Tumours, Treated With Lanreotide Autogel Given as Self 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

The subject was asked: 'Does the treatment administration used today interfere with your daily activities?'

The subject was asked: 'Does the treatment administration used today negatively interfere with your psychological wellbeing?'

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).

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.

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.

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.

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.

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.

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?

The training period was where the subject or partner performed two or three training injections under supervision of a HCP at a healthcare provider facility.

Training Period

The self or partner administration block (after training period) included three unsupervised injections every 28th day at the subject's home.

Self or Partner Administration

A healthcare administration block included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.

HCP Administration

Self or partner administration followed by HCP administration.

Group 1 Self or Partner First Then HCP Administration

Administration by HCP then self or partner administration.

Group 2 HCP Then Self or Partner Administration

Age, Categorical

Denmark

Norway

Sweden

Region of Enrollment

Medical Director, Endocrinology

Self or Partner Administration followed by HCP Administration.

Administration by HCP then Self or Partner Administration.

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

Subject Preference for Self or Partner Administration

Number of Patients Stating at Least One Injection Interfered With Daily Activities

Number of Patients Stating at Least One Injection Negatively Interfered With Psychological Wellbeing

The self or partner administration block (after the training period) included three unsupervised injections every 28th day at the subject's home.

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.

Days Sick Leave

The self or partner administration block (after the training) included three unsupervised injections every 28th day at the subject's home.

Safety population: all randomised subjects with at least one dose of study medication

Total Number of Visits to HCP Due to Carcinoid Symptoms

Worsened

Similar

Improved

Missing

Baseline refers to the last non-study visit at the clinic.

Baseline

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.

Perceived Symptom Control Evaluation in Respect to Episodes of Flushing

Perceived Symptom Control Evaluation in Respect to Episodes of Diarrhoea

Before self or partner administration block (after training period) which included three unsupervised injections every 28th day at the subject's home.

Before Self or Partner Administration

After the self or partner administration block which included three unsupervised injections every 28th day at the subject's home.

After Self or Partner Administration

Before the healthcare administration block which included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.

Before HCP Administration

After the healthcare administration block which included three HCP provided injections according to clinical routine every 28th day at the healthcare provider facility.

After HCP Administration

ITT population that had hormone levels assessed at each administration block.

Chromogranin A Levels

5-HIAA were assessed as judged necessary by the investigator at each site.

5-hydroxyindoleacetic Acid (5-HIAA) Levels

One HCP from each site who enrolled participants answered the questions

Overall Study Group

One HCP from each site who enrolled participants replied to the question

Healthcare Professionals With Positive Response to Specified Questions on Self or Partner Administration Method

Started with a training period where the subject or partner performed two or three training injections under supervision of a Healthcare Professional (HCP) at a healthcare provider facility. The training injections were followed by a self administration block of three subsequent unsupervised injections every 28th day at the subject's home. A healthcare administration block followed the self administration block with three HCP provided injections according to clinical routine every 28th day.

Started with a healthcare administration block with three HCP provided injections according to clinical routine every 28th day. A training period followed the healthcare administration block with two or three training injections performed by the subject or partner under supervision at the healthcare provider facilities. A self-administration block followed the training injections with 3 subsequent unsupervised injections every 28th day at the subject's home. The subject visited the clinic for a follow-up visit 14 days after the last self-partner administered injection.

Overall Study

Gland and Hormone Related Diseases

Digestive System Diseases

Endocrine Gland Neoplasms

Adenoma

Adenoma, Islet Cell

Endocrine System Diseases

Neoplasms, Glandular and Epithelial

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Pancreatic Neuroendocrine Tumor

Pancreatic Cancer

Patients from the preceding DB study (Study 726) were treated with open label lanreotide Autogel 120 mg by deep subcutaneous injections every 28 days. Patients were included if they had been treated with lanreotide (Autogel formulation) or placebo in DB Study 726 and had stable disease at the end of the 96-week treatment period, or if they had received placebo and had disease progression at any time during Study 726. Safety data were based on the safety population patients who received lanreotide in Study 729). The main efficacy analysis was based on the ITT population (patients randomised in Study 726 regardless of whether they continued into Study 729).

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).

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).

Study of Lanreotide Autogel 120 mg in Patients With Non-functioning Entero- Pancreatic Endocrine Tumour

Open Label Extension Study of Lanreotide Autogel 120 mg in Patients With Non-functioning Entero-pancreatic Endocrine Tumour

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

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.

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.

Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.

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.

Lanreotide Autogel

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.

All patients treated with lanreotide 120 mg (Autogel formulation) in the open label study.

Asian

Black or African American

Caucasian/White

Safety Population: All patients who received at least one dose of lanreotide Autogel in Study 729.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumours	NCT02683941	Neuroendocrine ...	Lanreotide (Aut... Placebo Best Supportive...	18 Years -	Ipsen
Somatuline Autogel Preference and Health Economy Study	NCT00681187	Neuroendocrine ...	lanreotide (Aut...	18 Years -	Ipsen
Study of Lanreotide Autogel 120 mg in Patients With Non-functioning Entero- Pancreatic Endocrine Tumour	NCT00842348	Non Functioning...	lanreotide (Aut...	18 Years -	Ipsen
Somatuline Autogel Preference and Health Economy Study	NCT00681187	Neuroendocrine ...	lanreotide (Aut...	18 Years -	Ipsen
Study of Lanreotide Autogel in Non-functioning Entero-pancreatic Endocrine Tumours	NCT00353496	Endocrine Tumor...	lanreotide (Aut... Placebo	18 Years -	Ipsen
Study of Lanreotide Autogel in Non-functioning Entero-pancreatic Endocrine Tumours	NCT00353496	Endocrine Tumor...	lanreotide (Aut... Placebo	18 Years -	Ipsen
Efficacy and Safety of Lanreotide Autogel in Tumour Stabilization of Patients With Progressive Neuroendocrine Tumours	NCT00326469	Neuroendocrine ...	lanreotide (Aut...	18 Years -	Ipsen

Spots Global Cancer Trial Database for lanreotide (autogel formulation)