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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-005579-10 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lanreotide (Autogel formulation) and Temozolomide | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lanreotide (Autogel formulation) and Temozolomide | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Disease Control Rate (DCR) Assessed Locally at Month 9 | 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 A sensitivity analysis-1 of local DCR was performed excluding participants withdrawn before 9 months with reason other than progressive disease (PD) or missing assessment and considering participants with PD prior or at 9 months as failures.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when 9-month assessment was missing using same methodology, i.e. considering PD prior or at 9 months and participants withdrawn with other or missing reasons as failures. | Up to Month 9; for sensitivity analysis-2, up to 10.5 months |
| Measure | Description | Time Frame |
|---|---|---|
| DCR Assessed Centrally at 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. | Up to Month 9 |
| Median Progression Free Survival (PFS) Assessed Locally and Centrally |
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Inclusion Criteria:
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:
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)
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oncologia Medica - Istituto Oncologico del Mediterraneo - IOM | Viagrande | Catania | 95029 | Italy | ||
| Unità Operativa di Oncologia Azienda Ospedaliera Spedali Civili di Brescia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36044870 | Derived | Ferolla P, Berruti A, Spada F, Brizzi MP, Ibrahim T, Marconcini R, Giuffrida D, Amoroso V, La Salvia A, Vaccaro V, Faggiano A, Colao A, Volante M, Ghizzoni S, Mazzanti P, Houchard A, Fazio N. Efficacy and Safety of Lanreotide Autogel and Temozolomide Combination Therapy in Progressive Thoracic Neuroendocrine Tumors (Carcinoid): Results from the Phase 2 ATLANT Study. Neuroendocrinology. 2023;113(3):332-342. doi: 10.1159/000526811. Epub 2022 Aug 31. |
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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.
This pilot study was conducted at 11 investigational sites in Italy between 06 July 2016 and 18 June 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lanreotide Autogel (ATG) Plus Temozolomide | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 16, 2017 | Aug 4, 2020 |
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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. |
| From Day 1 up to end of study, 52 weeks |
| Median Time to Response (TTR) Assessed Locally and Centrally | 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. | From Day 1 up to end of study, 52 weeks |
| Median Duration of Response (DOR) Assessed Locally and Centrally | 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. | From Day 1 up to end of study, 52 weeks |
| Median Time to Progression (TTP) Assessed Locally and Centrally | 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. | From Day 1 up to end of study, 52 weeks |
| Best Overall Response (BOR) Assessed Locally and Centrally | 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. | From Day 1 up to end of study, 52 weeks |
| Objective Response Rate (ORR) Assessed Locally and Centrally at 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. | Months 9 and 12 |
| DCR Assessed Locally and Centrally at 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. | Month 12 |
| DCR Assessed Locally and Centrally at Month 9 by Carcinoid Type | 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. | Up to Month 9 |
| Percentage of Biochemical Responders According to Chromogranin A (CgA) Plasma Levels | 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. | Baseline (Day 1) and Week 4, 12, 24, 36 and 52 |
| Neuron-Specific Enolase (NSE) and CgA Biomarker Levels | 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. | Baseline and Weeks 4, 12, 24, 36 and 52 |
| Influence of Biomarkers Expression on Locally and Centrally Assessed PFS | 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. | From Screening period (-4 weeks) up to Week 52 |
| Influence of Biomarkers Expression on Locally and Centrally Assessed ORR at 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. | Screening period, Months 9 and 12 |
| Influence of Biomarkers Expression on Locally and Centrally Assessed DCR at 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. | Screening period, Months 9 and 12 |
| Coefficient of Agreement Between Central and Local Assessment of Tumor Radiological Response at 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. | Month 9 |
| Brescia |
| 25123 |
| Italy |
| Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) S.r.l., IRCCS | Meldola | 47014 | Italy |
| Unità Oncologia Medica Gastrointestinale e Tumori Neuroendocrini Istituto Europeo di Oncologia, IEO | Milan | 20141 | Italy |
| Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica , Università degli Studi | Naples | 80131 | Italy |
| Dipartimento di Oncologia Università di Torino Ospedale San Luigi Gonzaga | Orbassano | 10043 | Italy |
| S.C di Oncologia Medica, Azienda Ospedaliera Universitaria di Perugia | Perugia | 06123 | Italy |
| U.O. Oncologia - Azienda Ospedaliero-Universitaria Pisana Ospedale S. Chiara | Pisa | 56126 | Italy |
| Oncologia Medica - Istituto Tumori Regina Elena San Gallicano | Roma | 00144 | Italy |
| OUC di Oncologia- Azienda Ospedaliera Universitaria Integrata - Ospedale Borgo Roma | Verona | 37134 | Italy |
| COMPLETED |
|
| NOT COMPLETED |
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The Intention-to-treat (ITT)/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Lanreotide ATG Plus Temozolomide | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants | No |
| |||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Disease Control Rate (DCR) Assessed Locally at Month 9 | 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | 95% Confidence Interval | percentage of participants | Up to Month 9; for sensitivity analysis-2, up to 10.5 months |
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| Secondary | DCR Assessed Centrally at 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | 95% Confidence Interval | percentage of participants | Up to Month 9 |
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| Secondary | Median Progression Free Survival (PFS) Assessed Locally and Centrally | 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Median | 95% Confidence Interval | weeks | From Day 1 up to end of study, 52 weeks |
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| Secondary | Median Time to Response (TTR) Assessed Locally and Centrally | 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Median | 95% Confidence Interval | weeks | From Day 1 up to end of study, 52 weeks |
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| Secondary | Median Duration of Response (DOR) Assessed Locally and Centrally | 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Median | 95% Confidence Interval | weeks | From Day 1 up to end of study, 52 weeks |
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| Secondary | Median Time to Progression (TTP) Assessed Locally and Centrally | 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Median | 95% Confidence Interval | weeks | From Day 1 up to end of study, 52 weeks |
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| Secondary | Best Overall Response (BOR) Assessed Locally and Centrally | 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | percentage of participants | From Day 1 up to end of study, 52 weeks |
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| Secondary | Objective Response Rate (ORR) Assessed Locally and Centrally at 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | 95% Confidence Interval | percentage of participants | Months 9 and 12 |
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| Secondary | DCR Assessed Locally and Centrally at 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | 95% Confidence Interval | percentage of participants | Month 12 |
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| Secondary | DCR Assessed Locally and Centrally at Month 9 by Carcinoid Type | 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | 95% Confidence Interval | percentage of participants | Up to Month 9 |
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| Secondary | Percentage of Biochemical Responders According to Chromogranin A (CgA) Plasma Levels | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline (Day 1) and Week 4, 12, 24, 36 and 52 |
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| Secondary | Neuron-Specific Enolase (NSE) and CgA Biomarker Levels | 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | percentage of participants | Baseline and Weeks 4, 12, 24, 36 and 52 |
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| Secondary | Influence of Biomarkers Expression on Locally and Centrally Assessed PFS | 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | 95% Confidence Interval | hazard ratio | From Screening period (-4 weeks) up to Week 52 |
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| Secondary | Influence of Biomarkers Expression on Locally and Centrally Assessed ORR at 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. | No analysis on ORR at 9 and 12 months was performed due to insufficient number of participants with OR events. | Posted | Screening period, Months 9 and 12 |
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| Secondary | Influence of Biomarkers Expression on Locally and Centrally Assessed DCR at 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | 95% Confidence Interval | odds ratio | Screening period, Months 9 and 12 |
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| Secondary | Coefficient of Agreement Between Central and Local Assessment of Tumor Radiological Response at 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. | The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide). | Posted | Number | 95% Confidence Interval | kappa coefficient | Month 9 |
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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.
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lanreotide ATG Plus Temozolomide | 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. | 9 | 40 | 9 | 40 | 38 | 40 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 21.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Blood thyroid stimulating hormone decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Blood thyroid stimulating hormone increased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Glucose tolerance decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Glycosylated haemoglobin increased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Vitamin b12 decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Vitamin d deficiency | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pleural thickening | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Angular cheilitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Bacteriuria | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Bile duct obstruction | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hepatic steatosis | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Tachyarrhythmia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Visual acuity reduced | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Breast mass | Reproductive system and breast disorders | MedDRA 21.1 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ipsen Medical Director | Ipsen | see email | clinical.trials@ipsen.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 4, 2020 | Aug 4, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| ID | Term |
|---|---|
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| C060347 | lanreotide |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Sensitivity analysis-2 |
|
|
| Binomial proportion test |
| <0.0001 |
One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 10%. |
| Other |
| Sensitivity Analyisis-1: Comparison of DCR to 30% clinically relevant threshold. | Binomial proportion test | 0.0534 | One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 30%. | Other |
| Sensitivity Analyisis-1: Comparison of DCR to 10% clinically relevant threshold. | Binomial proportion test | <0.0001 | One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 10%. | Other |
| Sensitivity Analyisis-2: Comparison of DCR to 30% clinically relevant threshold. | Binomial proportion test | 0.032 | One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 30%. | Other |
| Sensitivity Analyisis-2: Comparison of DCR to 10% clinically relevant threshold. | Binomial proportion test | <0.0001 | One-sided p-value estimated using an exact binomial proportion test for one-way tables comparing DCR to 10%. | Other |
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| Participants |
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| Participants |
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