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.

Hellenic Cooperative Oncology Group12 sites in 1 country25 target enrollmentAugust 6, 2012

ConditionsGastrointestinal Tumors Pancreatic Tumors Gastrointestinal Neuroendocrine Tumors Pancreatic Neuroendocrine Tumors

InterventionsEverolimus

DrugsEverolimus

Overview

Phase: Phase 2
Intervention: Everolimus
Conditions: Gastrointestinal Tumors
Sponsor: Hellenic Cooperative Oncology Group
Enrollment: 25
Locations: 12
Primary Endpoint: 15 month PFS (Progression-Free Survival) rate
Status: Terminated
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

August 6, 2012

End Date

August 6, 2019

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hellenic Cooperative Oncology Group

Responsible Party

Sponsor

Eligibility Criteria

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.

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)

Arms & Interventions

Everolimus

Intervention: Everolimus

Outcomes

Primary Outcomes

15 month PFS (Progression-Free Survival) rate

Time Frame: 15 months

To determine the rate of PFS patients at 15 months of treatment.

Secondary Outcomes

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.)
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)
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.)