Clinical trial NCT02248012: Everolimus and Temozolomide in Advanced Gastroenteropancreatic Neuroendocrine Carcinoma (G3)
Official title: Everolimus and Temozolomide as 1-line Treatment in Advanced Gastroenteropancreatic Neuroendocrine Carcinoma (G3) With a Ki67 of 20-55%
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Carcinoma
Keywords: Gastroenteropancreatic
Neuroendocrine carcinoma
Chemotherapy
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: Skane University Hospital
name: Copenhagen University Hospital, Denmark
name: Rigshospitalet, Denmark
name: Uppsala University Hospital
name: Aarhus University Hospital
name: Sahlgrenska University Hospital
name: Ullevaal University Hospital
First posted: 2014-09-25
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Disease control rate
timeFrame: 6 months
Secondary outcomes:
measure: Number of patients with adverse events
timeFrame: During treatment + 30 days
Other outcomes:
measure: Time (months) from start of study treatment to death (survival)
timeFrame: Average 14 months
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
Study officials:
affiliation: Haukeland Univ Hospital
name: Halfdan Sorbye, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sorbye H, Strosberg J, Baudin E, Klimstra DS, Yao JC. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer. 2014 Sep 15;120(18):2814-23. doi: 10.1002/cncr.28721. Epub 2014 Apr 25.