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An expanded access study of everolimus in patients with advanced neuroendocrine tumors.

Conditions
The study will evaluate the safety of everolimus in patients with advanced neuroendocrine tumors of gastrointestinal, lung or pancreatic origin.
MedDRA version: 14.0Level: PTClassification code 10052399Term: Neuroendocrine tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2010-023032-17-IT
Lead Sponsor
OVARTIS FARMA
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
400
Inclusion Criteria

1. Age = 18 years old; 2. Advanced (unresectable or metastatic) biopsy-proven neuroendocrine tumor of gastrointestinal, lung or pancreatic origin; 3. Performance Status 0-2 on the WHO scale; 4. Adequate bone marrow function as shown by: • ANC = 1.5 x 109/L, • Platelets = 100 x 109/L, • Hemoglobin >9 g/dL; 5. Adequate liver function as shown by: • Serum bilirubin = 1.5 x ULN, • ALT and AST = 2.5 x ULN. Patients with known liver metastases who have an AST and ALT = 5 x ULN, • INR < 1.3 (INR < 3 in patients treated with anticoagulants); 6. Adequate renal function as shown by: serum creatinine = 1.5 x ULN; 7. Fasting serum cholesterol = 300 mg/dL OR = 7.75 mmol/L AND fasting triglycerides = 2.5 x ULN; 8. Written informed consent obtained before any trial related activity and according to local guidelines.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma are not eligible; 2. Cytotoxic chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to enrollment; 3. Hepatic artery embolization within the last 2 months or cryoablation or radiofrequency ablation of hepatic metastasis within 2 months of enrollment; 4. Prior therapy with mTOR inhibitors (for example sirolimus, temsirolimus, everolimus); 5. Patients with a known hypersensitivity to everolimus or other rapamycin analogs (sirolimus, temsirolimus), or to its excipients; 6. Patients receiving chronic treatment with immunosuppressives; 7. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN; 8. Patients who have any severe and/or uncontrolled medical conditions such as: • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 6 months prior to enrollment, serious uncontrolled cardiac arrhythmia, • active or uncontrolled severe infection, • Patients with a history of invasive fungal infections, • severe hepatic impairment (Child-Pugh class C), • severely impaired lung function; 9. Active bleeding diathesis; 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 other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for = 3 years; 12. Patients within 4 weeks 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 of reproductive potential who are not using effective birth control methods. Adequate contraceptives must be used throughout the trial and for 8 weeks after last study drug administration in female patients. Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to first administration of study drug; 15. Patients unwilling to or unable to comply with the protocol.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To evaluate additional safety of everolimus in patients with advanced neuroendocrine tumors of gastrointestinal, lung or pancreatic origin.;Secondary Objective: - To evaluate investigator-assessed best overall response in patients with advanced NETs of gastrointestinal, lung or pancreatic origin treated with everolimus; - To estimate investigator-assessed progression free survival (PFS); - To provide expanded access to everolimus in patients with advanced NETs of gastrointestinal, lung or pancreatic origin; - To assess disease related symptoms and changes in health related quality of life (HRQoL) over time in advanced neuroendocrine patients treated with everolimus.;Primary end point(s): To evaluate the safety of everolimus: grade 3 or 4 adverse events, serious adverse events, laboratory abnormalities of CTC grade 3 or 4.;Timepoint(s) of evaluation of this end point: 15 months or until disease progression, unacceptable toxicity, death, discontinuation from the study for any other reason.
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): - To evaluate investigator-assessed best overall response in patients with advanced NETs of gastrointestinal, lung or pancreatic origin treated with everolimus; - To estimate investigator-assessed progression free survival (PFS); - To provide expanded access to everolimus in patients with advanced NETs of gastrointestinal, lung or pancreatic origin; - To assess disease related symptoms and changes in health related quality of life (HRQoL) over time in advanced neuroendocrine patients treated with everolimus.;Timepoint(s) of evaluation of this end point: 15 months or until disease progression, unacceptable toxicity, death, discontinuation from the study for any other reason.
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