An open-label, multi-center, expanded access study of everolimus in patients with advanced neuroendocrine tumors

• Register: EUCTR
• Last refreshed on: 15 July 2013
• Main ID: EUCTR2010-023032-17-DE
• Date of registration: 03/02/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: An open-label, multi-center, expanded access study of everolimus in patients with advanced neuroendocrine tumors
• Scientific title: An open-label, multi-center, expanded access study of everolimus in patients with advanced neuroendocrine tumors
• Date of first enrolment: 05/04/2011
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023032-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Germany, Greece, Italy, Portugal, Sweden

Key inclusion & exclusion criteria

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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

The study will evaluate the safety of everolimus in patients with advanced neuroendocrine tumors of gastrointestinal, lung or pancreatic origin.

Intervention(s)

Trade Name: Afinitor 5 mg Tabletten
Product Name: everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Afinitor 5 mg Tabletten
Product Name: everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

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

Main Objective: To evaluate additional safety of everolimus in patients with advanced neuroendocrine tumors of gastrointestinal, lung or pancreatic origin.

Primary end point(s): Safety:
grade 3 or 4 adverse events, serious adverse events

Secondary ID(s)

CRAD001K24133