ATLANT: Efficacy and Safety of Lanreotide Autogel (ATG) in Combination With Temozolomide in Subjects With Thoracic Neuroendocrine Tumors.

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02698410
• Collaborator: (none)
• Enrollment: 40
• Locations: 10
• Arm: 1
• Duration (Months): 35.5
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the protocol is to evaluate the efficacy and safety of Lanreotide ATG 120 mg in combination with Temozolomide in subjects with unresectable advanced neuroendocrine tumours of the lung or thymus as Disease Control Rate at 9 months.

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumours	Drug: Lanreotide (Autogel formulation) and Temozolomide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Lanreotide ATG 120 mg in Combination With Temozolomide in Subjects With Progressive Well Differentiated Thoracic Neuroendocrine Tumors. A Phase II, Multicentre, Single Arm, Open-label Trial.
• Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Feb 8, 2019
• Actual Study Completion Date: Jun 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lanreotide (Autogel formulation) and Temozolomide Lanreotide ATG 120 mg every 28 days, deep subcutaneous injection for a maximum of 48 weeks, for a total number of 12 injections. Temozolomide 250 mg hard capsules, for 5 consecutive days every 28 days, oral route, for a maximum of 48 weeks.	Drug: Lanreotide (Autogel formulation) and Temozolomide

Outcome Measures

Primary Outcome Measures

1. Disease Control Rate (DCR) Assessed Locally at Month 9 [Up to Month 9; for sensitivity analysis-2, up to 10.5 months]

   Responders were participants who showed disease control according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v 1.1 assessed locally by the investigator. The DCR was defined as complete response (CR), partial response (PR) or stable disease (SD) according to RECIST criteria v1.1. A sensitivity analysis-1 of local DCR was performed excluding participants withdrawn before 9 months with reason other than progressive disease (PD) or missing assessment and considering participants with PD prior or at 9 months as failures. In addition, a sensitivity analysis-2 was performed in order to consider assessments done between 7.5 and 10.5 months as 9 months assessments when 9-month assessment was missing using same methodology, i.e. considering PD prior or at 9 months and participants withdrawn with other or missing reasons as failures.

Secondary Outcome Measures

1. DCR Assessed Centrally at Month 9 [Up to Month 9]

   The DCR was defined as SD, PR or CR according to RECIST criteria v1.1. A second set of the original computed tomography (CT) scan images were used for a centralized RECIST v1.1 assessment by an independent radiologist.

2. Median Progression Free Survival (PFS) Assessed Locally and Centrally [From Day 1 up to end of study, 52 weeks]

   The PFS was defined as the time from the first treatment administration to disease progression according to RECIST criteria v 1.1 or death from any cause. The PFS was assessed locally by the investigator and centrally by an independent radiologist. The distribution of PFS times was estimated using the Kaplan-Meier method. The PFS of participants who were lost to follow-up and those who had not progressed at end of study were censored at the date of the last disease assessment.

3. Median Time to Response (TTR) Assessed Locally and Centrally [From Day 1 up to end of study, 52 weeks]

   The TTR was defined as the time from first treatment administration to the first objective tumor response (PR or CR according to RECIST criteria v 1.1). The TTR was assessed locally by the investigator and centrally by an independent radiologist. The distribution of TTR was estimated using the Kaplan-Meier method. The TTR of participants who were lost to follow-up or died prior to any objective tumor response were censored at the date of the last disease assessment.

4. Median Duration of Response (DOR) Assessed Locally and Centrally [From Day 1 up to end of study, 52 weeks]

   The DOR was defined as the time from onset of the first objective tumor response (PR or CR) to objective tumor progression (PD) according to RECIST criteria v 1.1. The DOR was assessed locally by the investigator and centrally by an independent radiologist.

5. Median Time to Progression (TTP) Assessed Locally and Centrally [From Day 1 up to end of study, 52 weeks]

   The TTP was defined as the time from first treatment administration to the first objective tumor progression (PD) according to RECIST criteria v 1.1. The TTP was assessed locally by the investigator and centrally by an independent radiologist. The distribution of TTP times was estimated using the Kaplan-Meier method. The TTP of participants who were lost to follow-up, and those who had not progressed at end of study were censored at the date of the last disease assessment.

6. Best Overall Response (BOR) Assessed Locally and Centrally [From Day 1 up to end of study, 52 weeks]

   The BOR was defined as the highest OR achieved by the participant from the time of first treatment until disease progression/recurrence or the end of study according to RECIST criteria v1.1 and was classified as: CR > PR > Non-CR/Non-progressive disease (NCR/NPD) > SD > PD > ND > not evaluable (NE). The BOR was assessed locally by the investigator and centrally by an independent radiologist. Percentages are based on the number of participants in the ITT/Safety population with non-missing observations.

7. Objective Response Rate (ORR) Assessed Locally and Centrally at Months 9 and 12 [Months 9 and 12]

   The ORR was defined as the percentage of participants with CR or PR according to RECIST criteria v1.1. The ORR was assessed locally by the investigator and centrally by an independent radiologist. The ORR was based on the participants with PD prior to 9 and 12 months with respectively PD at 9 and 12 months, and participants withdrawn before the assessment for reason other than PD or missing as failures.

8. DCR Assessed Locally and Centrally at Month 12 [Month 12]

   The DCR was defined as SD, PR or CR according to RECIST criteria v1.1. The DCR was assessed locally by the investigator and centrally by an independent radiologist.

9. DCR Assessed Locally and Centrally at Month 9 by Carcinoid Type [Up to Month 9]

   The influence of type of carcinoid [typical, atypical and undetermined carcinoid neuroendocrine tumors (NET)] on the local and central DCR at 9 months was analysed. Typical carcinoids were defined with absent foci of necrosis and mitotic count < 2 mitoses/2 millimeters^2 (mm^2); atypical carcinoids were defined with presence of foci of necrosis and/or 2 mitoses/2 mm^2 <= mitotic count <= 10 mitoses/2 mm^2; and carcinoid NET were defined as confirmed carcinoid without foci of necrosis and/or mitotic count reported. The DCR was assessed locally by the investigator and centrally by an independent radiologist.

10. Percentage of Biochemical Responders According to Chromogranin A (CgA) Plasma Levels [Baseline (Day 1) and Week 4, 12, 24, 36 and 52]

    Participants with baseline CgA plasma levels greater than the upper limit of normal (ULN) were assessed for a biochemical response. A biochemical responder was defined as a participant who had a decrease of CgA >= 50% compared to baseline, while biochemical SD was defined as a decrease < 50% or an increase <= 25% compared to baseline. Biochemical non-responders had an increase >25% compared to baseline. Baseline was defined as value at Day 1.

11. Neuron-Specific Enolase (NSE) and CgA Biomarker Levels [Baseline and Weeks 4, 12, 24, 36 and 52]

    The NSE and CgA levels were classified according to ULN as follows: < 1 ULN, 1-2 ULN and > 2 ULN. Baseline was defined as value at Day 1. Percentages are based on the number of participants in the ITT/Safety population who attended the visit with non-missing observations.

12. Influence of Biomarkers Expression on Locally and Centrally Assessed PFS [From Screening period (-4 weeks) up to Week 52]

    The following biomarkers were investigated: Immunohistochemistry assay human somatostatin receptors 2 (SSTR2) including human epidermal growth factor receptor 2 (HER-2) score [0, 1+, 2+, 3+ and positive (+ve) versus negative (-ve)]; hormone receptor score (H-score) (from 0 to 300 as quantitative variable and +ve versus -ve); immunoreactive score (IRS) score (from 0 to 12 and reference for hazard ratio was 0-1). Ki67 index (from 0% to 100% and reference for hazard ratio was 4%-25%). O^6-methylguanine-DNA methyltransferase (MGMT) expression including percentage of +ve nuclei stained and methylated sites and H-score (from 0 to 300 as quantitative variable). For all these categories, higher score indicates a higher expression of biomarkers. Carcinoid type (typical or NET) was also investigated. Prognostic value of biomarkers expression at screening on PFS were assessed locally and centrally using univariate cox proportional hazard models.

13. Influence of Biomarkers Expression on Locally and Centrally Assessed ORR at Months 9 and 12 [Screening period, Months 9 and 12]

    The following biomarkers were investigated: Immunohistochemistry assay SSTR2 including HER-2 score (0, 1+, 2+, 3+); H-score (from 0 to 300 as quantitative variable); IRS score (from 0 to 12). Ki67 index (from 0% to 100%). MGMT expression including percentage of +ve nuclei stained and methylated sites and H-score (from 0 to 300 as quantitative variable). For all these categories, higher score indicates a higher expression of biomarkers. Less than 5 OR (CR or PR) events were reported, therefore this analysis was not performed.

14. Influence of Biomarkers Expression on Locally and Centrally Assessed DCR at Months 9 and 12 [Screening period, Months 9 and 12]

    The following biomarkers were investigated: Immunohistochemistry assay SSTR2 including HER-2 score (0, 1+, 2+, 3+ and +ve versus -ve); H-score (from 0 to 300 as quantitative variable and +ve versus -ve); IRS score (from 0 to 12 and reference for odds ratio was 0-1). Ki67 index (from 0% to 100% and reference for odds ratio was 4%-25%). MGMT expression including percentage of +ve nuclei stained and methylated sites and H-score (from 0 to 300 as quantitative variable). For all these categories, higher score indicates a higher expression of biomarkers. Carcinoid type (typical or NET) was also investigated. Prognostic value of biomarkers expression at screening on DCR were assessed locally and centrally using univariate logistic regression models.

15. Coefficient of Agreement Between Central and Local Assessment of Tumor Radiological Response at Month 9 [Month 9]

    Differences between central radiology review and local investigator review were assessed according to the DCR status and the number of agreements and disagreements between the evaluators (central versus local) along with the p-values from the kappa test. A kappa statistic was used to evaluate the concordance between the central and the local review.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histological documented unresectable advanced (locally or metastatic) well or moderately differentiated neuroendocrine tumors of the lung or thymus (typical and atypical carcinoids according to the World Health Organisation (WHO) 2004 criteria);

• Imaging documented progression within 12 months before screening visit (V1), according to RECIST criteria v 1.1;

• Measurable disease, as defined by RECIST criteria v 1.1, on a CT scan performed at screening visit (V1);

• Octreoscan or Ga68-DOTA-TATE/TOC/NOC-PET-TC within 12 months before screening visit (V1);

• Adequate liver, renal and bone marrow function.

Exclusion Criteria:

• Poorly differentiated neuroendocrine carcinoma and mixed Neuroendocrine tumours (NET), according to WHO 2004 criteria

• Neuroendocrine tumours other than lung or thymus

• Non-neuroendocrine thymic neoplasm

• Received a prior therapy with Peptide Receptor Radionuclide Therapy (PRRT) within 6 months prior to screening visit (V1)

• Treated with systemic therapies (chemotherapy, interferon-alpha, somatostatin analogues, molecular target therapies) within 1 month prior to screening visit (V1)

• Treated with a number of systemic therapy lines > 3 prior to screening visit (V1), and any of the following:

1. for chemotherapy no more than 1 line prior to V1

2. for somatostatin analogue no more than 1 line therapy, considered as treatment lasting more than 6 months, prior to V1 no therapy with Temozolomide (TMZ) prior to V1

3. Received a prior therapy with Peptide Receptor Radionuclide Therapy (PRRT) within 6 months prior to screening visit (V1)

• Received external palliative radiotherapy within the last 28 days prior to screening visit (V1)

• Received locoregional therapies (Transarterial embolization, Transcatheter arterial chemoembolization, thermo-ablation with radio-frequency) and Selective internal radiotherapy within 3 months prior to screening visit (V1)

• Presence of symptomatic brain metastasis

• Subjects with symptomatic cholelithiasis at screening visit (V1)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oncologia Medica - Istituto Oncologico del Mediterraneo - IOM	Viagrande	Catania	Italy	95029
2	Unità Operativa di Oncologia Azienda Ospedaliera Spedali Civili di Brescia	Brescia		Italy	25123
3	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) S.r.l., IRCCS	Meldola		Italy	47014
4	Unità Oncologia Medica Gastrointestinale e Tumori Neuroendocrini Istituto Europeo di Oncologia, IEO	Milan		Italy	20141
5	Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica , Università degli Studi	Napoli		Italy	80131
6	Dipartimento di Oncologia Università di Torino Ospedale San Luigi Gonzaga	Orbassano		Italy	10043
7	S.C di Oncologia Medica, Azienda Ospedaliera Universitaria di Perugia	Perugia		Italy	06123
8	U.O. Oncologia - Azienda Ospedaliero-Universitaria Pisana Ospedale S. Chiara	Pisa		Italy	56126
9	Oncologia Medica - Istituto Tumori Regina Elena San Gallicano	Roma		Italy	00144
10	OUC di Oncologia- Azienda Ospedaliera Universitaria Integrata - Ospedale Borgo Roma	Verona		Italy	37134

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

• Study Protocol - Nov 16, 2017
• Statistical Analysis Plan - May 4, 2020

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT02698410
• Other Study ID Numbers: A-93-52030-325; 2014-005579-10
• First Posted: Mar 3, 2016
• Last Update Posted: Oct 1, 2020
• Last Verified: Sep 1, 2020

• Additional relevant MeSH terms: Neuroendocrine Tumors; Temozolomide; Lanreotide

Study Results

Participant Flow

Recruitment Details	This pilot study was conducted at 11 investigational sites in Italy between 06 July 2016 and 18 June 2019.
Pre-assignment Detail	The study consisted of a screening period (maximum 4 weeks), followed by an open label treatment period of up to a maximum of 52 weeks or until disease progression, death or unacceptable toxicity, or subject/physician decision.

Arm/Group Title	Lanreotide Autogel (ATG) Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 milligrams (mg) was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Period Title: Overall Study
STARTED	40
COMPLETED	36
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Overall Participants	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (11.8)
Sex: Female, Male (Count of Participants)
Female	16 40%
Male	24 60%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	40 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Disease Control Rate (DCR) Assessed Locally at Month 9
Description	Responders were participants who showed disease control according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v 1.1 assessed locally by the investigator. The DCR was defined as complete response (CR), partial response (PR) or stable disease (SD) according to RECIST criteria v1.1. A sensitivity analysis-1 of local DCR was performed excluding participants withdrawn before 9 months with reason other than progressive disease (PD) or missing assessment and considering participants with PD prior or at 9 months as failures. In addition, a sensitivity analysis-2 was performed in order to consider assessments done between 7.5 and 10.5 months as 9 months assessments when 9-month assessment was missing using same methodology, i.e. considering PD prior or at 9 months and participants withdrawn with other or missing reasons as failures.
Time Frame	Up to Month 9; for sensitivity analysis-2, up to 10.5 months

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
DCR at Month 9	35.0 87.5%
Sensitivity analysis-1	45.2 113%
Sensitivity analysis-2	45.0 112.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lanreotide ATG Plus Temozolomide
	Comments	Comparison of DCR to 30% clinically relevant threshold.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2968
	Comments	One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 30%.
	Method	Binomial proportion test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lanreotide ATG Plus Temozolomide
	Comments	Comparison of DCR to 10% clinically relevant threshold.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 10%.
	Method	Binomial proportion test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lanreotide ATG Plus Temozolomide
	Comments	Sensitivity Analyisis-1: Comparison of DCR to 30% clinically relevant threshold.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0534
	Comments	One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 30%.
	Method	Binomial proportion test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lanreotide ATG Plus Temozolomide
	Comments	Sensitivity Analyisis-1: Comparison of DCR to 10% clinically relevant threshold.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 10%.
	Method	Binomial proportion test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lanreotide ATG Plus Temozolomide
	Comments	Sensitivity Analyisis-2: Comparison of DCR to 30% clinically relevant threshold.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.032
	Comments	One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 30%.
	Method	Binomial proportion test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lanreotide ATG Plus Temozolomide
	Comments	Sensitivity Analyisis-2: Comparison of DCR to 10% clinically relevant threshold.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 10%.
	Method	Binomial proportion test
	Comments

2. Secondary Outcome

Title	DCR Assessed Centrally at Month 9
Description	The DCR was defined as SD, PR or CR according to RECIST criteria v1.1. A second set of the original computed tomography (CT) scan images were used for a centralized RECIST v1.1 assessment by an independent radiologist.
Time Frame	Up to Month 9

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	28.2 70.5%

3. Secondary Outcome

Title	Median Progression Free Survival (PFS) Assessed Locally and Centrally
Description	The PFS was defined as the time from the first treatment administration to disease progression according to RECIST criteria v 1.1 or death from any cause. The PFS was assessed locally by the investigator and centrally by an independent radiologist. The distribution of PFS times was estimated using the Kaplan-Meier method. The PFS of participants who were lost to follow-up and those who had not progressed at end of study were censored at the date of the last disease assessment.
Time Frame	From Day 1 up to end of study, 52 weeks

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Local assessment	37.1
Central assessment	37.1

4. Secondary Outcome

Title	Median Time to Response (TTR) Assessed Locally and Centrally
Description	The TTR was defined as the time from first treatment administration to the first objective tumor response (PR or CR according to RECIST criteria v 1.1). The TTR was assessed locally by the investigator and centrally by an independent radiologist. The distribution of TTR was estimated using the Kaplan-Meier method. The TTR of participants who were lost to follow-up or died prior to any objective tumor response were censored at the date of the last disease assessment.
Time Frame	From Day 1 up to end of study, 52 weeks

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Local assessment	NA
Central assessment	NA

5. Secondary Outcome

Title	Median Duration of Response (DOR) Assessed Locally and Centrally
Description	The DOR was defined as the time from onset of the first objective tumor response (PR or CR) to objective tumor progression (PD) according to RECIST criteria v 1.1. The DOR was assessed locally by the investigator and centrally by an independent radiologist.
Time Frame	From Day 1 up to end of study, 52 weeks

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Local assessment	NA
Central assessment	NA

6. Secondary Outcome

Title	Median Time to Progression (TTP) Assessed Locally and Centrally
Description	The TTP was defined as the time from first treatment administration to the first objective tumor progression (PD) according to RECIST criteria v 1.1. The TTP was assessed locally by the investigator and centrally by an independent radiologist. The distribution of TTP times was estimated using the Kaplan-Meier method. The TTP of participants who were lost to follow-up, and those who had not progressed at end of study were censored at the date of the last disease assessment.
Time Frame	From Day 1 up to end of study, 52 weeks

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Local assessment	37.1
Central assessment	37.1

7. Secondary Outcome

Title	Best Overall Response (BOR) Assessed Locally and Centrally
Description	The BOR was defined as the highest OR achieved by the participant from the time of first treatment until disease progression/recurrence or the end of study according to RECIST criteria v1.1 and was classified as: CR > PR > Non-CR/Non-progressive disease (NCR/NPD) > SD > PD > ND > not evaluable (NE). The BOR was assessed locally by the investigator and centrally by an independent radiologist. Percentages are based on the number of participants in the ITT/Safety population with non-missing observations.
Time Frame	From Day 1 up to end of study, 52 weeks

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	39
Local assessment: CR	0 0%
Local assessment: PR	7.7 19.3%
Local assessment: SD	71.8 179.5%
Local assessment: NCR/NPD	0 0%
Local assessment: PD	20.5 51.3%
Local assessment: NE	0 0%
Local assessment: Not applicable	0 0%
Central assessment: CR	0 0%
Central assessment: PR	13.2 33%
Central assessment: SD	65.8 164.5%
Central assessment: NCR/NPD	2.6 6.5%
Central assessment: PD	15.8 39.5%
Central assessment: NE	0 0%
Central assessment: Not applicable	2.6 6.5%

8. Secondary Outcome

Title	Objective Response Rate (ORR) Assessed Locally and Centrally at Months 9 and 12
Description	The ORR was defined as the percentage of participants with CR or PR according to RECIST criteria v1.1. The ORR was assessed locally by the investigator and centrally by an independent radiologist. The ORR was based on the participants with PD prior to 9 and 12 months with respectively PD at 9 and 12 months, and participants withdrawn before the assessment for reason other than PD or missing as failures.
Time Frame	Months 9 and 12

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Local assessment: Month 9	2.5 6.3%
Local assessment: Month 12	2.5 6.3%
Central assessment: Month 9	5.1 12.8%
Central assessment: Month 12	2.6 6.5%

9. Secondary Outcome

Title	DCR Assessed Locally and Centrally at Month 12
Description	The DCR was defined as SD, PR or CR according to RECIST criteria v1.1. The DCR was assessed locally by the investigator and centrally by an independent radiologist.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Local assessment	17.5 43.8%
Central assessment	15.4 38.5%

10. Secondary Outcome

Title	DCR Assessed Locally and Centrally at Month 9 by Carcinoid Type
Description	The influence of type of carcinoid [typical, atypical and undetermined carcinoid neuroendocrine tumors (NET)] on the local and central DCR at 9 months was analysed. Typical carcinoids were defined with absent foci of necrosis and mitotic count < 2 mitoses/2 millimeters^2 (mm^2); atypical carcinoids were defined with presence of foci of necrosis and/or 2 mitoses/2 mm^2 <= mitotic count <= 10 mitoses/2 mm^2; and carcinoid NET were defined as confirmed carcinoid without foci of necrosis and/or mitotic count reported. The DCR was assessed locally by the investigator and centrally by an independent radiologist.
Time Frame	Up to Month 9

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Local assessment: Typical carcinoid	12.5 31.3%
Local assessment: Atypical carcinoid	47.6 119%
Local assessment: Carcinoid NET	27.3 68.3%
Central assessment: Typical carcinoid	0 0%
Central assessment: Atypical carcinoid	35.0 87.5%
Central assessment: Carcinoid NET	36.4 91%

11. Secondary Outcome

Title	Percentage of Biochemical Responders According to Chromogranin A (CgA) Plasma Levels
Description	Participants with baseline CgA plasma levels greater than the upper limit of normal (ULN) were assessed for a biochemical response. A biochemical responder was defined as a participant who had a decrease of CgA >= 50% compared to baseline, while biochemical SD was defined as a decrease < 50% or an increase <= 25% compared to baseline. Biochemical non-responders had an increase >25% compared to baseline. Baseline was defined as value at Day 1.
Time Frame	Baseline (Day 1) and Week 4, 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). Only participants with baseline CgA levels greater than ULN were analysed.

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	24
Week 4: Responders	27.3 68.3%
Week 4: SD	59.1 147.8%
Week 4: Non-responders	13.6 34%
Week 12: Responders	37.5 93.8%
Week 12: SD	37.5 93.8%
Week 12: Non-responders	25.0 62.5%
Week 24: Responders	23.1 57.8%
Week 24: SD	30.8 77%
Week 24: Non-responders	46.2 115.5%
Week 36: Responders	36.4 91%
Week 36: SD	27.3 68.3%
Week 36: Non-responders	36.4 91%
Week 52: Responders	12.5 31.3%
Week 52: SD	50.0 125%
Week 52: Non-responders	37.5 93.8%

12. Secondary Outcome

Title	Neuron-Specific Enolase (NSE) and CgA Biomarker Levels
Description	The NSE and CgA levels were classified according to ULN as follows: < 1 ULN, 1-2 ULN and > 2 ULN. Baseline was defined as value at Day 1. Percentages are based on the number of participants in the ITT/Safety population who attended the visit with non-missing observations.
Time Frame	Baseline and Weeks 4, 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
CgA: Baseline: <1 ULN	40.0 100%
CgA: Baseline: 1-2 ULN	15.0 37.5%
CgA: Baseline: >2 ULN	45.0 112.5%
CgA: Week 4: <1 ULN	34.3 85.8%
CgA: Week 4: 1-2 ULN	22.9 57.3%
CgA: Week 4: >2 ULN	42.9 107.3%
CgA: Week 12: <1 ULN	46.4 116%
CgA: Week 12: 1-2 ULN	17.9 44.8%
CgA: Week 12: >2 ULN	35.7 89.3%
CgA: Week 24: <1 ULN	30.0 75%
CgA: Week 24: 1-2 ULN	25.0 62.5%
CgA: Week 24: >2 ULN	45.0 112.5%
CgA: Week 36: <1 ULN	31.3 78.3%
CgA: Week 36: 1-2 ULN	12.5 31.3%
CgA: Week 36: >2 ULN	56.3 140.8%
CgA: Week 52: <1 ULN	27.3 68.3%
CgA: Week 52: 1-2 ULN	9.1 22.8%
CgA: Week 52: >2 ULN	63.6 159%
NSE: Baseline: <1 ULN	65.0 162.5%
NSE: Baseline: 1-2 ULN	25.0 62.5%
NSE: Baseline: >2 ULN	10.0 25%
NSE: Week 4: <1 ULN	62.9 157.3%
NSE: Week 4: 1-2 ULN	25.7 64.3%
NSE: Week 4: >2 ULN	11.4 28.5%
NSE: Week 12: <1 ULN	78.6 196.5%
NSE: Week 12: 1-2 ULN	17.9 44.8%
NSE: Week 12: >2 ULN	3.6 9%
NSE: Week 24: <1 ULN	80.0 200%
NSE: Week 24: 1-2 ULN	10.0 25%
NSE: Week 24: >2 ULN	10.0 25%
NSE: Week 36: <1 ULN	87.5 218.8%
NSE: Week 36: 1-2 ULN	6.3 15.8%
NSE: Week 36: >2 ULN	6.3 15.8%
NSE: Week 52: <1 ULN	63.6 159%
NSE: Week 52: 1-2 ULN	18.2 45.5%
NSE: Week 52: >2 ULN	18.2 45.5%

13. Secondary Outcome

Title	Influence of Biomarkers Expression on Locally and Centrally Assessed PFS
Description	The following biomarkers were investigated: Immunohistochemistry assay human somatostatin receptors 2 (SSTR2) including human epidermal growth factor receptor 2 (HER-2) score [0, 1+, 2+, 3+ and positive (+ve) versus negative (-ve)]; hormone receptor score (H-score) (from 0 to 300 as quantitative variable and +ve versus -ve); immunoreactive score (IRS) score (from 0 to 12 and reference for hazard ratio was 0-1). Ki67 index (from 0% to 100% and reference for hazard ratio was 4%-25%). O^6-methylguanine-DNA methyltransferase (MGMT) expression including percentage of +ve nuclei stained and methylated sites and H-score (from 0 to 300 as quantitative variable). For all these categories, higher score indicates a higher expression of biomarkers. Carcinoid type (typical or NET) was also investigated. Prognostic value of biomarkers expression at screening on PFS were assessed locally and centrally using univariate cox proportional hazard models.
Time Frame	From Screening period (-4 weeks) up to Week 52

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Local: SSTR2: HER-2 score; +ve (2+, 3+)	0.71
Local: SSTR2: H-score; +ve (>= 50)	0.66
Local: SSTR2: IRS score; 2-3	0.31
Local: SSTR2: IRS score; 4-8	0.90
Local: SSTR2: IRS score; 9-12	0.12
Local: Ki67: <4	1.08
Local: Ki67: >=25	1.68
Local: MGMT: +ve nuclei stained; +ve (>=5%)	2.06
Local: MGMT: Methylated sites; +ve (>10%)	0.41
Local: MGMT: H-score	1.00
Local: Carcinoid type: Typical	1.05
Local: Carcinoid type: Carcinoid NET	1.59
Central: SSTR2: HER-2 score; +ve (2+, 3+)	0.50
Central: SSTR2: H-score; +ve (>= 50)	0.36
Central: SSTR2: IRS score; 2-3	0.78
Central: SSTR2: IRS score; 4-8	0.88
Central: SSTR2: IRS score; 9-12	0.10
Central: Ki67: <4	0.00
Central: Ki67: >=25	2.75
Central: MGMT: +ve nuclei stained; +ve (>=5%)	2.11
Central: MGMT: Methylated sites; +ve (>10%)	0.73
Central: MGMT: H-score	1.00
Central: Carcinoid type: Typical	0.99
Central: Carcinoid type: Carcinoid NET	0.61

14. Secondary Outcome

Title	Influence of Biomarkers Expression on Locally and Centrally Assessed ORR at Months 9 and 12
Description	The following biomarkers were investigated: Immunohistochemistry assay SSTR2 including HER-2 score (0, 1+, 2+, 3+); H-score (from 0 to 300 as quantitative variable); IRS score (from 0 to 12). Ki67 index (from 0% to 100%). MGMT expression including percentage of +ve nuclei stained and methylated sites and H-score (from 0 to 300 as quantitative variable). For all these categories, higher score indicates a higher expression of biomarkers. Less than 5 OR (CR or PR) events were reported, therefore this analysis was not performed.
Time Frame	Screening period, Months 9 and 12

Outcome Measure Data

Analysis Population Description

No analysis on ORR at 9 and 12 months was performed due to insufficient number of participants with OR events.

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	0

15. Secondary Outcome

Title	Influence of Biomarkers Expression on Locally and Centrally Assessed DCR at Months 9 and 12
Description	The following biomarkers were investigated: Immunohistochemistry assay SSTR2 including HER-2 score (0, 1+, 2+, 3+ and +ve versus -ve); H-score (from 0 to 300 as quantitative variable and +ve versus -ve); IRS score (from 0 to 12 and reference for odds ratio was 0-1). Ki67 index (from 0% to 100% and reference for odds ratio was 4%-25%). MGMT expression including percentage of +ve nuclei stained and methylated sites and H-score (from 0 to 300 as quantitative variable). For all these categories, higher score indicates a higher expression of biomarkers. Carcinoid type (typical or NET) was also investigated. Prognostic value of biomarkers expression at screening on DCR were assessed locally and centrally using univariate logistic regression models.
Time Frame	Screening period, Months 9 and 12

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Month 9: Local: SSTR2: HER-2 score; +ve (2+, 3+)	0.90
Month 9: Local: SSTR2: H-score; +ve (>= 50)	0.78
Month 9: Local: SSTR2: IRS score; 2-3	NA
Month 9: Local: SSTR2: IRS score; 4-8	0.67
Month 9: Local: SSTR2: IRS score; 9-12	12.00
Month 9: Local: Ki67: <4	NA
Month 9: Local: Ki67: >=25	1.67
Month 9:Local: MGMT: +ve nuclei stained; +ve(>=5%)	NA
Month 9: Local: MGMT: Methylated sites; +ve (>10%)	3.25
Month 9: Local: MGMT: H-score	0.99
Month 9: Local: Carcinoid type: Typical	0.16
Month 9: Local: Carcinoid type: Carcinoid NET	0.41
Month 9: Central: SSTR2: HER-2 score; +ve (2+, 3+)	1.40
Month 9: Central: SSTR2: H-score; +ve (>= 50)	2.25
Month 9: Central: SSTR2: IRS score; 2-3	3.00
Month 9: Central: SSTR2: IRS score; 4-8	0.67
Month 9: Central: SSTR2: IRS score; 9-12	12.00
Month 9: Central: Ki67: <4	NA
Month 9: Central: Ki67: >=25	NA
Month 9:Central:MGMT:+ve nuclei stained; +ve(>=5%)	0.50
Month 9:Central: MGMT: Methylated sites; +ve(>10%)	5.00
Month 9: Central: MGMT: H-score	1.00
Month 9: Central: Carcinoid type: Typical	NA
Month 9: Central: Carcinoid type: Carcinoid NET	1.06
Month 12: Local: SSTR2: HER-2 score; +ve (2+, 3+)	3.00
Month 12: Local: SSTR2: H-score; +ve (>= 50)	4.40
Month 12: Local: SSTR2: IRS score; 2-3	NA
Month 12: Local: SSTR2: IRS score; 4-8	0.70
Month 12: Local: SSTR2: IRS score; 9-12	10.50
Month 12: Local: Ki67: <4	NA
Month 12: Local: Ki67: >=25	NA
Month 12:Local:MGMT: +ve nuclei stained; +ve(>=5%)	0.20
Month 12: Local: MGMT: Methylated sites; +ve(>10%)	2.13
Month 12: Local: MGMT: H-score	0.99
Month 12: Local: Carcinoid type: Typical	0.46
Month 12: Local: Carcinoid type: Carcinoid NET	0.32
Month 12: Central: SSTR2: HER-2 score; +ve(2+, 3+)	2.08
Month 12: Central: SSTR2: H-score; +ve (>= 50)	3.00
Month 12: Central: SSTR2: IRS score; 2-3	NA
Month 12: Central: SSTR2: IRS score; 4-8	NA
Month 12: Central: SSTR2: IRS score; 9-12	10.50
Month 12: Central: Ki67: <4	NA
Month 12: Central: Ki67: >=25	NA
Month 12:Central:MGMT:+ve nuclei stained;+ve(>=5%)	0.14
Month 12:Central: MGMT: Methylated sites;+ve(>10%)	3.00
Month 12: Central: MGMT: H-score	0.99
Month 12: Central: Carcinoid type: Typical	0.57
Month 12: Central: Carcinoid type: Carcinoid NET	0.40

16. Secondary Outcome

Title	Coefficient of Agreement Between Central and Local Assessment of Tumor Radiological Response at Month 9
Description	Differences between central radiology review and local investigator review were assessed according to the DCR status and the number of agreements and disagreements between the evaluators (central versus local) along with the p-values from the kappa test. A kappa statistic was used to evaluate the concordance between the central and the local review.
Time Frame	Month 9

Outcome Measure Data

Analysis Population Description

The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
Measure Participants	40
Number (95% Confidence Interval) [kappa coefficient]	0.71

Adverse Events

Time Frame	Treatment-emergent adverse events were collected from the start of the first treatment (Day 1) until 4 weeks after the end of the last study treatment, up to a maximum of 52 weeks.
Adverse Event Reporting Description	The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). All-cause mortality occurred in both treatment period and follow-up period were reported.
Arm/Group Title	Lanreotide ATG Plus Temozolomide
Arm/Group Description	Lanreotide ATG 120 mg was administered by deep subcutaneous injection on Day 1 (baseline) and every 28 days for up to 52 weeks. Participants also received temozolomide 250 mg capsule orally once daily for 5 consecutive days every 28 days for up to 52 weeks. The dose of temozolomide could subsequently be reduced to 180 mg daily for 5 consecutive days every 28 days in case of bone marrow toxicity.
All Cause Mortality
	Lanreotide ATG Plus Temozolomide
	Affected / at Risk (%)	# Events
Total	9/40 (22.5%)
Serious Adverse Events
	Lanreotide ATG Plus Temozolomide
	Affected / at Risk (%)	# Events
Total	9/40 (22.5%)
General disorders
Death	1/40 (2.5%)	1
Non-cardiac chest pain	1/40 (2.5%)	1
Pain	1/40 (2.5%)	1
Hepatobiliary disorders
Cholecystitis	1/40 (2.5%)	1
Infections and infestations
Diverticulitis	1/40 (2.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/40 (2.5%)	1
Nervous system disorders
Nervous system disorder	1/40 (2.5%)	1
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/40 (2.5%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	Lanreotide ATG Plus Temozolomide
	Affected / at Risk (%)	# Events
Total	38/40 (95%)
Blood and lymphatic system disorders
Anaemia	2/40 (5%)	2
Lymphopenia	1/40 (2.5%)	1
Neutropenia	1/40 (2.5%)	1
Thrombocytopenia	1/40 (2.5%)	1
Cardiac disorders
Bradycardia	1/40 (2.5%)	1
Tachyarrhythmia	1/40 (2.5%)	1
Ear and labyrinth disorders
Vertigo	1/40 (2.5%)	1
Eye disorders
Visual acuity reduced	1/40 (2.5%)	1
Gastrointestinal disorders
Nausea	21/40 (52.5%)	42
Vomiting	13/40 (32.5%)	24
Diarrhoea	12/40 (30%)	36
Constipation	8/40 (20%)	26
Abdominal pain	2/40 (5%)	2
Abdominal pain upper	1/40 (2.5%)	1
Dry mouth	1/40 (2.5%)	1
Haematochezia	1/40 (2.5%)	1
Stomatitis	1/40 (2.5%)	1
Toothache	1/40 (2.5%)	1
General disorders
Asthenia	8/40 (20%)	8
Pyrexia	6/40 (15%)	6
Pain	4/40 (10%)	4
Influenza like illness	3/40 (7.5%)	3
Fatigue	2/40 (5%)	4
Chest pain	1/40 (2.5%)	1
Oedema peripheral	1/40 (2.5%)	1
Hepatobiliary disorders
Cholelithiasis	2/40 (5%)	3
Bile duct obstruction	1/40 (2.5%)	1
Hepatic steatosis	1/40 (2.5%)	1
Infections and infestations
Urinary tract infection	2/40 (5%)	2
Angular cheilitis	1/40 (2.5%)	1
Bacteriuria	1/40 (2.5%)	1
Ear infection	1/40 (2.5%)	1
Fungal infection	1/40 (2.5%)	1
Gastroenteritis	1/40 (2.5%)	1
Influenza	1/40 (2.5%)	1
Oral herpes	1/40 (2.5%)	1
Pharyngitis	1/40 (2.5%)	1
Investigations
Weight decreased	7/40 (17.5%)	7
Blood cholesterol increased	4/40 (10%)	5
Platelet count decreased	4/40 (10%)	7
Blood creatinine increased	3/40 (7.5%)	3
Aspartate aminotransferase increased	2/40 (5%)	2
Blood thyroid stimulating hormone decreased	2/40 (5%)	2
Blood triglycerides increased	2/40 (5%)	2
Gamma-glutamyltransferase increased	2/40 (5%)	2
Lymphocyte count decreased	2/40 (5%)	5
White blood cell count decreased	2/40 (5%)	3
Alanine aminotransferase increased	1/40 (2.5%)	1
Blood thyroid stimulating hormone increased	1/40 (2.5%)	1
Glucose tolerance decreased	1/40 (2.5%)	1
Glycosylated haemoglobin increased	1/40 (2.5%)	1
Neutrophil count decreased	1/40 (2.5%)	1
Transaminases increased	1/40 (2.5%)	1
Vitamin b12 decreased	1/40 (2.5%)	1
Metabolism and nutrition disorders
Hyperglycaemia	5/40 (12.5%)	6
Hypocalcaemia	2/40 (5%)	2
Type 2 diabetes mellitus	2/40 (5%)	2
Vitamin d deficiency	2/40 (5%)	2
Decreased appetite	1/40 (2.5%)	1
Hypercalcaemia	1/40 (2.5%)	1
Hypercholesterolaemia	1/40 (2.5%)	1
Hyperkalaemia	1/40 (2.5%)	1
Hyperuricaemia	1/40 (2.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	5/40 (12.5%)	5
Musculoskeletal pain	4/40 (10%)	4
Arthralgia	3/40 (7.5%)	4
Musculoskeletal chest pain	3/40 (7.5%)	3
Pain in extremity	3/40 (7.5%)	4
Pain in jaw	1/40 (2.5%)	1
Nervous system disorders
Headache	4/40 (10%)	5
Sciatica	2/40 (5%)	2
Dysgeusia	1/40 (2.5%)	1
Paraesthesia	1/40 (2.5%)	1
Psychiatric disorders
Anxiety	1/40 (2.5%)	1
Depression	1/40 (2.5%)	1
Insomnia	1/40 (2.5%)	1
Renal and urinary disorders
Dysuria	1/40 (2.5%)	1
Reproductive system and breast disorders
Breast mass	1/40 (2.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	5/40 (12.5%)	6
Dyspnoea	3/40 (7.5%)	3
Dyspnoea exertional	1/40 (2.5%)	1
Haemoptysis	1/40 (2.5%)	1
Pleural thickening	1/40 (2.5%)	1
Pneumonitis	1/40 (2.5%)	1
Productive cough	1/40 (2.5%)	1
Skin and subcutaneous tissue disorders
Rash	3/40 (7.5%)	5
Pruritus	2/40 (5%)	2
Erythema	1/40 (2.5%)	1
Hyperhidrosis	1/40 (2.5%)	1
Vascular disorders
Flushing	2/40 (5%)	2
Hypertension	2/40 (5%)	3
Hypotension	1/40 (2.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Results are owned by the Sponsor and data communication collected in a center by the investigator is allowed only after publication of aggregate results of the study by the Sponsor. If an investigator intends to communicate data, the Sponsor must be informed and should review the manuscript/publication before its submission. The investigator should accept any Sponsor comments provided they are not in contrast to the reliability of data, with rights, with the safety and well-being of patients.