Everolimus and temozolomide as first-line treatment in advanced gastrointestinal neuroendocrine carcinoma (G3) with a Ki67 of 20-55% MedDRA version: 21.0 Level: LLT Classification code 10062476 Term: Neuroendocrine tumor System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Temozolomide
Product Name: Temozolomide
Product Code: ATC: L01A X03
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomide
Other descriptive name: TEMOZOLOMIDE
Concentration
Sponsors
Dept of Oncology. Haukeland University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Histology and staging disease: •Histologically proven neuroendocrine carcinoma with a Ki67 of 20-55% by local pathology review. •Primary gastrointestinal tumor or cancer of unknown primary when metastases are mainly GI. •The patient cannot by surgery be rendered free from disease General conditions: •>18 years; •WHO performance status 1. •Adequate haematological function •Adequate renal and hepatic functions: •Written informed consent prior to inclusion must be obtained and documented according to the local regulatory requirements •Measurable disease according to RECIST criteria v 1.1. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: •Prior chemotherapy for advanced/metastatic disease. •Adjuvant chemotherapy must have ended > 6 months before inclusion. •Pregnancy or breast-feeding. Fertile patients must use adequate contraception. •Other anti-cancer systemic treatment within the last 8 weeks, including other experimental drugs. •Chronic infectious or immunosuppressive disease including, but not limited to, HIV, HCV and HBV. •Uncontrolled diabetes mellitus defined as HbA1c = 8% despite adequate therapy. •Known hypersensitivity to temozolomide or everolimus, or related compounds. •Patients receiving chronic treatment with corticosteroids or other immunosuppressive agents. •Other serious medical condition or illness that according to the investigator could be negatively affected by the study treatment. •Patients with history of another primary malignancy within the last 3 years, with the exception of locally treated non-melanoma skin cancer and carcinoma in situ of the uterine cervix. •Patients that can be expected to not be able to comply to study treatment. •Patients using significant inducers or inhibitors of CYP3A4 or P-glycoprotein (PgP) substrates 2 weeks prior to start of study medications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To study the efficacy of everolimus combined with temozolomide as first-line treatment in advanced gastrointestinal neuroendocrine carcinoma with a Ki67 of 20-55%, measured as disease control rate (non-progressive disease) at 6 months.;Secondary Objective: To assess: •Overall survival •Progression free survival •Objective response rate •Response duration •Safety profile •Quality of life using EORTC QLQ-C30 ;Primary end point(s): Disease control rate (CR+PR+SD) at six months according to RECIST-criteria (version 1.1). ;Timepoint(s) of evaluation of this end point: Baseline CT scans must be taken within 15 days prior to start of treatment. First CT evaluation must be performed after 6 weeks on treatment. Thereafter patients should be evaluated every 8th (+/- 2) week. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Objective response rates (CR+PR) according to RECIST v 1.1 Duration of response defined as time from objective response to progression of disease. Progression-free survival defined as time from study inclusion until progression of disease or death from any cause. Overall survival defined as time from study inclusion until death from any cause. Toxicity according to NCI CTCAE-criteria (v 4.0). Quality of life as measured with EORTC QLQ-C30. ;Timepoint(s) of evaluation of this end point: Adverse events and symptoms: Every 4th (+/- 1) week from start of treatment. Serum bio-markers (CgA and others): within 14 days prior to start of study treatment. After 6 (+/- 1) weeks from start of treatment, then every 8th (+/- 2) week Blood sample (full blood + serum) for biobank (to be frozen)within 14 days prior to start of study treatment and after 6 weeks of treatment. QoL within 14 days prior to start of study treatment and after 6 weeks from start of treatment, then every 8th week Somatostatin receptor imaging: Within 6 weeks prior to inclusion or within 6 weeks after inclusion. FDG-PET : Before start of treatment and after 6 weeks of treatment | — |
Countries
Denmark, Sweden
Contacts
Public ContactDept of Oncology. Haukeland Univ
Nordic Neuroendocrine Tumor Group
Outcome results
None listed