To determine whether treatment with RAD001 10 mg/d plus Sandostatin LAR® prolongs the progression free survival (PFS) compared to treatment with Sandostatin LAR® alone in patients with advanced carcinoid tumor.
ID
Source
Brief title
Condition
- Endocrine and glandular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective is to compare the progression-free survival (based on the
central radiological assessment). The primary efficacy variable
progression-free survival will be analyzed using both Intention to Treat (ITT)
and per protocol population. The analysis result of the ITT population using
the central radiological assessment is considered as the primary analysis.
Secondary outcome
Secondary efficacy variables include best overall response rate, the duration
of overall response (CR or PR) and of overall complete response (CR), overall
survival and otherefficacy markers. Best overall response rate will be assessed
by RECIST criteria.
Background summary
Low grade neuroendocrine carcinoma consists of carcinoid and pancreatic
endocrine tumors
A recent increase in the incidence of carcinoid tumors have been detected.
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 metastatic tumors have either low biologic activity, high
unfavorable toxicity profile or both.
For carcinoid, despite the many chemotherapy trials that have been conducted,
no regimen has demonstrated a response rate of more than 15%. Interferon has
also been widely studied in this disease. While octreotide has a role in the
management of carcinoid syndrome, objective tumor responses are rare.
RAD001 has a potential to act directly on the tumor cells by inhibiting tumor
cell growth anad proliferation. On the other hand RAD001 has also a potential
to act indirectly by inhibiting angiogenesis leading to reduced tumor
vascularity.
Study objective
To determine whether treatment with RAD001 10 mg/d plus Sandostatin LAR®
prolongs the progression free survival (PFS) compared to treatment with
Sandostatin LAR® alone in patients with advanced carcinoid tumor.
Study design
This is a prospective, randomized, double-blind, multicenter,
placebo-controlled, parallel group phase III study to evaluate the safety and
efficacy of RAD001 10 mg/day or matching placebo plus Sandostatin LAR® in
patients with advanced carcinoid tumor.
Intervention
Treatment arm 1: RAD001 (everolimus) 10 mg/d along with Sandostatin LAR® Depot
30mg every 28 days
Treatment arm 2: Placebo along with Sandostatin LAR® Depot 30mg every 28 days
Study burden and risks
Toxicity of RAD001 alone or of the combination of RAD001 and Sandostatine LAR.
Radiation exposure of CT-scans.
Obtaining blood samples may cause some discomfort, bruising, bleeding from the
site of sampling, formation of a blood clot, and, in rare cases, infection.
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
1. Advanced (unresectable or metastatic) biopsy-proven carcinoid tumor.
2. Confirmed low-grade or intermediate-grade neuroendocrine carcinoma
3. Radiological documentation of progression of disease within 12 months prior to randomization
4. Measurable disease CTscan or MRI
5. Adequate bone marrow function (ANC * 1.5 x 109/L, Platelets * 100 x 109/L, Hb >9 g/dL)
6. Adequate liver function:
* serum bilirubin * 1.5 x ULN
* INR < 1.3 x ULN (or < 3 on anticoagulants)
* ALT and AST * 2.5x ULN (* 5x ULN in patients with liver metastases)
7. Adequate renal function: serum creatinine * 1.5 x ULN
8. Fasting serum cholesterol *300 mg/dL OR 7.75 mmol/L AND fasting triglycerides * 2.5 x ULN. Treatment with lipid lowering agents is allowed.
9. WHO performance 0-2
Exclusion criteria
1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine
carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma
2. Cytotoxic chemotherapy, immunotherapy or radiotherapy < 4 weeks prior to randomization
3. Received treatment with Sandostatin LAR® Depot or any other long-acting somatostatin
analog < 2 weeks prior to randomization.
4. Hepatic artery embolization < the last 6 months (1 month if there are other sites of
measurable disease), or cryoablation of hepatic metastasis < 2 months of randomization
5. Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus)
6. Uncontrolled diabetes mellitus (fasting serum glucose >1.5 X ULN)
7. Severe and/or uncontrolled medical conditions such as:
* unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction
* 6 months prior to randomization, serious cardiac arrhythmia,
* severe infection
* cirrhosis, chronic (active) hepatitis
* severely impaired lung function
8. Chronic treatment with corticosteroids or another immunosuppressive agent
9. Patients with a known history of HIV seropositivity
10. Patients with an active, bleeding diathesis
11. History of another primary malignancy * 3 years, except non-melanoma skin cancer, and carcinoma in situ of uterine cervix
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-004507-18-NL |
| ClinicalTrials.gov | NCT00412061 |
| CCMO | NL16050.042.07 |