OPALINE : A Study Of Morbidity And Mortality At 2 Years

Study Overview
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Brief Summary
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A descriptive, prospective (partly retrospective), multisite, observational study conducted in France in adult patients treated for a well differentiated, unresectable or metastatic, pancreatic neuroendocrine tumor with disease progression.

Detailed Description
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prospective and retrospective Analyses will be performed using SAS® software

Official Title
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AN OBSERVATIONAL REAL-WORLD STUDY OF THE SYSTEMIC TREATMENT OF WELL-DIFFERENTIATED, UNRESECTABLE OR METASTATIC, PROGRESSIVE PANCREATIC NEUROENDOCRINE TUMOURS (PNET): A STUDY OF MORBIDITY AND MORTALITY AT 2 YEARS

Conditions
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Pancreatic Neuroendocrine Tumor, Well Differentiated and Progressive

Intervention / Treatment
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* Drug: sunitinib
* Drug: everolimus
* Drug: chemotherapies recommended in france


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years of age; Patients treated with a targeted therapy (sunitinib, everolimus) or with other treatments (interferon, or metabolic radiotherapy, or chemotherapy or somatostatin analog)* for: *Patients whose treatment line (targeted therapy or other treatment) is initiated as a 1st, 2nd, 3rd or 4th line of therapy at the time of inclusion (incident patients) or patients receiving their 1st, 2nd, 3rd or 4th line of therapy provided that treatment was initiated in the site in which the patient is enrolled in the study (prevalent patients); a change of line is defined as a change in molecule or combination. A histologically confirmed unresectable or metastatic pancreatic neuroendocrine tumor; Well-differentiated; Progressive prior to initiation of treatment in the investigator's judgment (clinical or radiological progression); Patients who have been informed of the conditions of the study and who have signed the informed consent. Exclusion Criteria: Patients with a diagnosis of poorly differentiated neuroendocrine carcinoma or an adenoneuroendocrine carcinoma. Patients receiving targeted therapy (everolimus or sunitinib) already received in a previous line of treatment (rechallenged patient). Patients refusing to give consent. Patients receiving a fifth line or subsequent line of systemic treatment. Patients participating in a clinical trial in a treatment arm not validated by the MA and the TNCD according to the version dated December 2013. Patients randomized to the placebo arm of a placebo-controlled trial or to a double-blind trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sunitinib<br> | Drug: sunitinib<br>* sunitinib 37.5mg/d orally<br>|
| Afinitor<br> | Drug: everolimus<br>* everolimus 10mg/d orally<br>|
| other treatment (chémotherapy, SSA..)<br> | Drug: chemotherapies recommended in france<br>* depends on the chemotherapy prescribed (IV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) at 2 Years Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 - Based on Type of Treatment at Inclusion | PFS was defined as time (in months) from date of start of treatment (the treatment line ongoing at the time of inclusion in the study) to first documentation of disease progression (PD) or date of death due to any cause, when receiving the main treatment at the time of inclusion. RECIST v1.1, PD: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study treatment (this included baseline sum if that is smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Unequivocal progression of existing non-target lesions. Appearance of 1 or more new target or non-target lesions. If a participant did not have an event, data censoring was done at the last recorded time to PD or the last tumor assessment, last disease assessment. Analysis was performed using Kaplan-Meier method. | At 2 years of prospective follow-up | 
| PFS at 2 Years Assessed by Investigator Per RECIST v1.1 - Based on Targeted Therapy Group and Other Treatments Group at Inclusion | PFS was defined as time (in months) from date of start of treatment (the treatment line ongoing at the time of inclusion in the study) to first documentation of PD or date of death due to any cause, when receiving the main treatment at the time of inclusion. RECIST v1.1, PD: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study treatment (this included baseline sum if that is smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of 1 or more new target or non-target lesions. If a participant did not have an event, data censoring was done at the last recorded time to PD or the last tumor assessment, last disease assessment. Analysis was performed using Kaplan-Meier method. | At 2 years of prospective follow-up | 
| Overall Survival (OS) Rate at 2 Years - Based on Type of Treatment at Inclusion | OS was the percentage of participants who were alive at 2 years of prospective follow-up. OS was defined as the time (in months) from the date of start of treatment (of the treatment line ongoing at the time of inclusion in the study) to the date of death due to any cause. Participants with no event or lost to follow-up or alive at the end of the study were censored at their last follow-up date (last follow-up date or last news). Analysis was performed using Kaplan-Meier method. | At 2 years of prospective follow-up | 
| OS Rate at 2 Years- Based on Targeted Therapy Group and Other Treatments Group at Inclusion | OS was the percentage of participants who were alive at 2 years of prospective follow-up. OS was defined as the time (in months) from the date of start of treatment (of the treatment line ongoing at the time of inclusion in the study) to the date of death due to any cause. Participants with no event or lost to follow-up or alive at the end of the study were censored at their last follow-up date (last follow-up date or last news). Analysis was performed using Kaplan-Meier method. | At 2 years of prospective follow-up | 
| Number of Participants With Reasons for Temporary and Permanent Treatment Discontinuation - Based on Targeted Therapy Group and Other Treatment Group at Inclusion |  | During 2 years of prospective follow-up | 
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs, SAEs and SAEs With Common Terminology Criteria For Adverse Events (CTCAE) 3, 4 and 5, v4.0-Based on Treatment Received At-least Once During Study | AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: any AE, regardless of dose, that: led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. Treatment-related AE was any untoward medical occurrence attributed to study drug in participant who received study drug. Relatedness to treatment was assessed by investigator. Per CTCAE 4.0, Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4=Life-threatening events Grade 5 (Death) events=death related to an AE. Participants in this outcome measure were grouped according to type of treatment received at least once during study irrespective of treatment they initiated or were receiving at time of inclusion. | During 2 years of prospective follow-up | 
| Number of Participants With Adverse Events Leading to Discontinuation of Treatment - Based on Treatment Received At-least Once During the Study | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Participants in this outcome measure were grouped according to type of treatment received at least once during study irrespective of treatment they initiated or were receiving at time of inclusion. | During 2 years of prospective follow-up | 
| Number of Participants With Adverse Events Leading to Death - Based on Treatment Received At-least Once During the Study | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Adverse events leading to death are reported in this outcome measure. Participants in this outcome measure were grouped according to type of treatment received at least once during study irrespective of treatment they initiated or were receiving at time of inclusion. | During 2 years of prospective follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of Number of Tumor Assessment Visits - Based on Targeted Therapy Group and Other Treatments Group at Inclusion |  | During 2 years of prospective follow-up | 
| Number of Participants According to Frequency of Tumor Assessment Visits - Based on Targeted Therapy Group and Other Treatments Group at Inclusion | Frequency = number of tumor assessment visits /([last visit date - baseline date]/365.25). | During 2 years of prospective follow-up | 
| Number of Participants With Different Types of Investigation Used for Tumor Assessment - Based on Targeted Therapy Group and Other Treatments Group at Inclusion | The different types of investigations were performed for assessment of tumor regardless of treatment received. Investigations performed were Computed Tomography (CT) scan, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) scan, Octreoscan, Ultrasound. All the investigations were used at least once during the study for all treatments. | During 2 years of prospective follow-up | 
| Number of Participants Who Had a Change in Their Treatment - Based on Targeted Therapy Group and Other Treatments Group at Inclusion | In this outcome measure, number of participants with a change in treatment compared to treatment at inclusion is reported. | During 2 years of prospective follow-up | 
| Number of Participants According to Number of Changes in Doses of Treatment - Based on Type of Treatment (Everolimus, Sunitinib, Chemotherapy and Somatostatin Analogues) at Inclusion | Number of participants according to number of changes in doses of treatment is reported for this outcome measure. | During 2 years of prospective follow-up | 
| Number of Participants According to Course of Changes in Doses of Treatment - Based on Type of Treatment (Metabolic Radiotherapy) at Inclusion | Number of participants according to course of changes in doses of treatment is reported for this outcome measure. | During 2 years of prospective follow-up | 
| Number of Combined Main Lines of Treatments Received - Based on Targeted Therapy Group and Other Treatments Group at Inclusion | The number of lines of combined main treatment administered during the study were assessed. | During 2 years of prospective follow-up | 
| Number of Main Lines of Treatment Received During the Study - Based on Targeted Therapy Group and Other Treatments Group at Inclusion | The number of main lines of treatment received during the study treatment are reported in this outcome measure. | During 2 years of prospective follow-up | 
| Number of Participants With Types of Main Lines of Treatment Received During the Follow-up - Based on Targeted Therapy Group and Other Treatments Group at Inclusion | The types of main lines of treatment included 1st line, 2nd line, 3rd line, 4th line, 5th line, 6th line, 7th line and 8th line. | During 2 years of prospective follow-up |