Everolimus and Temozolomide in Advanced Gastroenteropancreatic Neuroendocrine Carcinoma (G3)

Study Overview
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Brief Summary
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To study the efficacy of everolimus combined with temozolomide as first-line treatment in advanced gastroenteropancreatic neuroendocrine carcinoma with a Ki67 of 20-55%, measured as disease control rate (non-progressive disease) at 6 months.

Detailed Description
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Guidelines for treating advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) advocate the use of combination chemotherapy with a platinum-based chemotherapy combined with etoposide. No other regimen has consistently shown a benefit over this combination. NECs do not respond to treatments usually applied in other neuroendocrine tumours such as somatostatin analogues and interferon. In contrast to metastatic neuroendocrine tumours with a low Ki67, debulking surgery and surgery for liver metastasis is generally not recommended. Cisplatin /carboplatin and etoposide is established as standard treatment of advanced disease based on two small retrospective studies showing a response rate between 41- 67% and median survival of 15-19 months. In the current trial we propose an alternative treatment for a subgroup of patients with GEP-NEC based on new data, with the intention to improve response rates and clinical benefit rate without increasing toxicity

Official Title
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Everolimus and Temozolomide as 1-line Treatment in Advanced Gastroenteropancreatic Neuroendocrine Carcinoma (G3) With a Ki67 of 20-55%

Conditions
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Neuroendocrine Carcinoma

Intervention / Treatment
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* Drug: Everolimus , temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Histologically proven neuroendocrine carcinoma with a Ki67 of 20-55%.Primary gastroenteropancreatic tumor or cancer of unknown primary where metastases are mainly abdominalMeasurable disease according to RECIST by CT/MR General conditions: >18 years; WHO/ECOG performance status 0-1. Adequate haematological, renal and hepatic functions: Written informed consent prior to inclusion Prior therapy: No prior chemotherapy treatment for advanced disease. Adjuvant chemotherapy must have ended > 6 months before inclusion. Prior or current history: No curatively resectable disease; No other serious illness or medical conditions (including: unstable angina, myocardial infarction within 6 months, unstable diabetes, immune suppression ) Concomitant treatments : No concomitant (or within 4 weeks before inclusion) administration of any other experimental drug; No other concurrent anti-cancer therapy. Other : Not pregnant or breast feeding. Fertile patients must use adequate contraceptives and fertile females must have a negative pregnancy test.

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus/temozolomide<br>Everolimus 10 mg daily, temozolomide 150 mg/m2 for 7 days every 2 weeks. | Drug: Everolimus , temozolomide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events | Especially number of patients with grade 3-4 toxicity. | During treatment + 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastroenteropancreatic, Neuroendocrine carcinoma, Chemotherapy