Study of Everolimus Treatment in Newly-diagnosed Patients With Advanced Gastrointestinal Neuroendocrine Tumors

Study Overview
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Brief Summary
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The purpose of this study is to explore the efficacy and safety of everolimus administered as a first-line treatment in newly-diagnosed patients with advanced or inoperable Gastrointestinal (GI) or pancreatic neuroendocrine tumors.

Official Title
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Phase II Multicenter Single-arm Study Evaluating the Safety and Efficacy of Everolimus as a First-line Treatment in Newly-diagnosed Patients With Advanced GI Neuroendocrine Tumors.

Conditions
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Gastrointestinal Tumors, Pancreatic Tumors, Gastrointestinal Neuroendocrine Tumors, Pancreatic Neuroendocrine Tumors

Intervention / Treatment
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* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged ≥ 18 years of age. Newly diagnosed patients with biopsy-proven well or moderately differentiated advanced (metastatic or unresectable) GI or pancreatic neuroendocrine tumor. Measurable disease based on RΕCIST 1.1 using a triphase CT scan or multi-phase MRI scan. Patients with a ki-67 measurement <20% prior to their enrollment to the study. Performance status 0-2 on the WHO scale. Adequate bone marrow function as shown by:ANC ≥ 1.5 x 10^9/L,Platelets ≥ 100 x 10^9/L,Hemoglobin > 9 g/dL. Adequate liver function as shown by:Serum bilirubin ≤ 1.5 x ULN,ALT/SGPT and AST/SGOT ≤ 2.5 x ULN (ή ≤ 5 x ULN in patients with known liver metastases),INR < 1.3 (INR < 3 in patients treated with anticoagulants). Adequate renal function as shown by: serum creatinine ≤ 1.5 x ULN. Fasting serum cholesterol ≤ 300 mg/dL or ≤ 7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN. Note: In case one or both the above upper limits are exceeded, patient enrollment can only be performed upon proper antilipidemic treatment initiation. Women of childbearing potential, with a negative serum or urine pregnancy test within 48 hours prior to first study treatment administration. Signed informed consent form obtained before any trial related activity, including the screening phase, according to the applicable law and ICH/GCP requirements. Signed informed consent for the use of biological and genetic material Exclusion Criteria: Patients with poorly differentiated or undifferentiated GI or pancreatic neuroendocrine carcinoma. Previous or concurrent cytotoxic chemotherapy, immunotherapy or radiotherapy. Hepatic artery embolization or cryoablation of hepatic metastasis within 1 month of study enrollment. Prior therapy with mTOR inhibitors (for example sirolimus, temsirolimus, everolimus). Patients receiving chronic treatment with corticosteroid immunosuppressives. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN. 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 < 50 %) active or uncontrolled severe infection cirrhosis, chronic active hepatitis, chronic persistent hepatitis or inadequate hepatic function (ALT/SGPT and AST/SGOT > 5 x ULN) inadequate bone marrow (ANC < 1.5 x 10^9/L, platelets < 100 x 10^9/L, hemoglobin ≤ 9 g/dL) or renal failure (serum creatinine > 1.5 x ULN severely impaired lung function (patients needing oxygen support). Active bleeding diathesis or on oral treatment with vitamin K antagonists (apart from low-dose coumadine). Performance status ≥ 3 on the WHO scale. Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required. 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. Patients within 28 days post-major surgery (e.g. intra-thoracic, intrabdominal 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. Female patients who are pregnant or nursing (lactating). 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. Patients participating in another clinical trial or receiving an investigational drug. Patients unwilling or unable to comply with the protocol at the investigator's discretion.

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<br> | Drug: Everolimus<br>* Everolimus 10mg(2x5mg)orally once daily until disease progression, unacceptable toxicity or consent withdrawal<br>* Other names: RAD001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 15 month PFS (Progression-Free Survival) rate | To determine the rate of PFS patients at 15 months of treatment. | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) |  | Defined as the time from the date of enrollment to the date of 1st radiologically documented disease progression or disease related death,assessed up to 36 months. | 
| Overall Survival (OS) |  | Defined as the time from the date of enrollment to the date of death from any cause,assessed up to 36 months. | 
| Evaluation of best response to treatment and the time to best response achievement |  | Defined as the period from the date of treatment initiation to best response observation date througout the study, assessed up to 15 months. | 
| Assessment of safety |  | Assessment of adverse events will be performed every 28 days (per cycle) during treatment, assessed up to 16 months. | 
| Association of biologic markers with disease progression |  | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic, unresectable, well or moderately differentiated, advanced