Well or moderately differentiated advanced (metastatic or unresectable) GI or pancreatic neuroendocrine tumors. MedDRA version: 14.1 Level: LLT Classification code 10062476 Term: Neuroendocrine tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Afinitor
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligra
Sponsors
Hellenic Cooperative Oncology Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female, aged =18 years of age. 2.Newly diagnosed patients with biopsy-proven well or moderately differentiated advanced (metastatic or unrectable) GI or pancreatic neuroendocrine tumor. 3.Measurable disease based on R?CIST 1.1 using a triphase CT scan or multi-phase MRI scan. 4.Patients with a ki-67 measurement prior to their enrollment to the study. 5.Performance status 0-2 on the WHO scale. 6.Adequate bone marrow function as shown by:ANC = 1.5 x 10^9/L,Platelets = 100 x 10^9/L,Hemoglobin >9 g/dL. 7.Adequate liver function as shown by:Serum bilirubin = 1.5 x ULN,ALT/SGPT and AST/SGOT = 2.5 x ULN (? = 5 x ULN in patients with known liver metastases),INR =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1.Patients with poorly differentiated or undifferentiated GI or pancreatic neuroendocrine carcinoma. 2.Previous or concurrent cytotoxic chemotherapy, immunotherapy or radiotherapy. 3.Hepatic artery embolization or cryoablation of hepatic metastasis within 1 month of study enrollment. 4.Prior therapy with mTOR inhibitors (for example sirolimus, temsirolimus, everolimus). 5.Patients receiving chronic treatment with corticosteroid immunosuppressives. 6.Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN. 7.Patients who have any severe and/or uncontrolled medical conditions such as: ·unstable angina pectoris, symptomatic congestive heart failure NYHA class II, III, IV, myocardial infarction = 6 months prior to enrollment, serious uncontrolled cardiac arrhythmia (LVEF 5 x ULN) ·inadequate bone marrow (ANC 1.5 x ULN ·severely impaired lung function (patients needing oxygen support). 8.Active bleeding diathesis or on oral treatment with vitamin K antagonists (apart from low-dose coumadine). 9.Performance status =3 on the WHO scale. 10.Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required. 11.No other prior or concurrent malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or treated in situ cancer of the cervix, or any other cancer from which the patient has been disease free for = 3 years. 12.Patients within 28 days post-major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy, or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device require 7 days prior to study entry. Note: Patients must have recovered from the acute effects of surgery prior to enrollment. 13.Female patients who are pregnant or nursing (lactating). 14.Adults with reproductive potential who are not using effective birth control methods. If barrier contraceptive measures are being used, these must be continued throughout the study by both sexes. 15.Patients participating in another clinical trial or receiving an investigational drug. 16.Patients unwilling or unable to comply with the protocol at the investigator’s discretion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate 15month progression-free survival rate (15month PFS rate) (according to RECIST 1.1) in newly-diagnosed patients with advanced or unresectable GI and pancreatic neuroendocrine tumors treated with everolimus as a first-line treatment. ;Secondary Objective: •To evaluate progression free survival (PFS) and overall survival (OS) •To evaluate best overall response during the study and the time to best overall response achievement. •To evaluate the safety of everolimus as a first-line treatment. •To evaluate the possible correlation between biomarkers and disease progression.;Primary end point(s): To evaluate the time of progression-free survival (PFS) and determine the rate of PFS patients at 15 months of treatment. ;Timepoint(s) of evaluation of this end point: 15 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1.Progression-free survival (PFS) is defined as the time from the date of enrollment to the date of the first radiologically documented disease progression or disease related death. 2.Defined as the time from the date of enrollment to the date of death from any cause. 3.Time to best overall response is defined as the period from the date of treatment initiation to the best response observation date throughout the study. 4. Assessment of adverse events (AEs) will be performed every 28 days (per cycle) during treatment 5. At study initiation, on day 1 of cycle 3, every 3 cycles thereafter and at the end of treatment;Secondary end point(s): 1. Evaluation of time to progression-free survival (PFS) 2. Evaluation of overall survival (OS) 3. Evaluation of best response during the study treatment and the time to best response achievement 4. Assessment of safety of everolimus as first line treatment 5. The association of biologic markers with disease progression | — |
Countries
Greece
Contacts
Public ContactClinical Trials
Hellenic Cooperative Oncology Group
Outcome results
None listed