A randomized, double-blind, placebo-controlled, multicenter phase III study in patients with advanced carcinoid tumor receiving Sandostatin LAR® Depot and RAD001 10 mg/d or Sandostatin LAR® Depot and placebo - N/A

Phase 1

• Conditions: ow grade neuroendocrine carcinoma consists of carcinoid and pancreatic endocrine tumors. These tumors originate from the neuroendocrine cells throughout the body and are capable of producing various peptides. Their clinical course is often indolent but can also be highly aggressive and resistant to therapy. Current treatments for bulky metastatic tumors have either low biologic activity, high unfavorable toxicity profile or both.; MedDRA version: 8.1Level: LLTClassification code 10007276Term: Carcinoid tumour NOS

• Registration Number: EUCTR2006-004507-18-DK
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-24
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 390

Inclusion Criteria

1. Advanced (unresectable or metastatic) biopsy-proven carcinoid tumor
2. Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma
3. Patients must have radiological documentation of progression of disease within 12 months prior to randomization
4. Measurable disease per RECIST determined by Triphasic Computer Tomography (CT) scan or MRI
5. Patients must have a history of secretory symptoms, which is defined as symptoms of diarrhea or flushing or both which were attributed to their carcinoid tumor. However, these symptoms need not be active at the time of enrollment.
6. Adequate bone marrow function as shown by: ANC = 1.5 x 10 high 9/L, Platelets = 100 x 10 high 9/L, Hb >9 g/dL
7. Adequate liver function as shown by:
• serum bilirubin = 1.5 x ULN
• INR < 1.3 (or < 3 on anticoagulants)
• ALT and AST = 2.5x ULN (= 5x ULN in patients with liver metastases)
8. Adequate renal function: serum creatinine = 1.5 x ULN
9. Fasting serum cholesterol =300 mg/dL OR = 7.75 mmol/L AND fasting triglycerides = 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
10. Performance Status 0-2 on the WHO scale
11. Adult male or female patients >or =18 years of age
12. Women of childbearing potential must have had a negative serum or urine pregnancy test within 48 hours prior to the administration of the first study treatment.
13. Patients who give a written informed consent obtained 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 randomization
3. Received treatment with Sandostatin LAR® Depot or any other long-acting somatostatin analog within 2 weeks prior to randomization.
4. Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation or radiofrequency ablation of hepatic metastasis within 2 months of randomization
5. Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus)
6. Known intolerance or hypersensitivity to octreotide, Sandostatin LAR, RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus)
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 randomization, serious uncontrolled cardiac arrhythmia
• active or uncontrolled severe infection
• cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air)
• active, bleeding diathesis
9. Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
10. Patients with a known history of HIV seropositivity
11. Patients who have a history of another primary malignancy = 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix
12. Female patients who are pregnant or nursing (lactating), or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes
13. Patients who have received an investigative drug or therapy within the last 30 days

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: • To evaluate the anti-tumor effect of RAD001 on other tumor endpoints (best overall response rate –Complete Response (CR) and Partial Response (PR), response duration)<br>• To compare overall survival (OS) between the study arms<br>• To compare changes from baseline in 5-hydroxyindoleacetic acid (5 HIAA) and chromogranin A (CgA) <br>• To determine the safety and tolerability of the combination of RAD001 (10 mg/d) plus Sandostatin LAR® Depot<br>• To characterize the pharmacokinetics of RAD001 and Sandostatin LAR® Depot administered in combination in carcinoid indications;Main Objective: To determine whether treatment with RAD001 10 mg/d plus Sandostatin LAR® Depot prolongs the progression free survival (PFS) compared to treatment with Sandostatin LAR® Depot alone in patients with advanced carcinoid tumor;Primary end point(s): progression-free survival