RAD001 Plus Octreotide Depot in Metastatic or Unresectable Low Grade Neuroendocrine Carcinoma
-Assess the clinical activity of RAD 001 plus depot octreotide as defined by progression free survival (PFS) duration defined by RECIST criteria in treated and untreated patients with metastatic, unresectable low grade neuroendocrine carcinoma.
- Assess the progression free survival duration of patients with metastatic, unresectable low grade neuroendocrine carcinoma treated with RAD 001 plus depot octreotide.
- Assess the safety of RAD 001 plus depot octreotide in patients with metastatic, unresectable low grade neuroendocrine carcinoma.
- To determine the expression/phosphorylation status of the components of the mTOR signaling pathway in the primary tumors, in order to determine whether these markers can be used as predictors of sensitivity to the combination of RAD001 and octreotide.
- To determine the effect of the combination of RAD001 and octreotide on the expression and phosphorylation of mTOR's targets in the accessible tumor tissue, in order to identify potential pharmacodynamics markers of response to this drug combination.
- To observe the effects of treatment with RAD001 on plasma angiogenic biomarkers.
|Neuroendocrine Carcinoma Islet Cell Carcinoma||Drug: RAD001 Drug: Octreotide Depot||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of RAD001 Plus Octreotide Depot in Patients With Metastatic or Unresectable Low Grade Neuroendocrine Carcinoma (Carcinoid, Islet Cell)|
- Progression Free Survival (PFS) [ Time Frame: PFS assessed every 12 weeks (at the end of every 3 cycles) or more frequently if clinically indicated ]PFS is measured from date of trial entry until documented progression of disease or death from any cause. PFS is measured by computed tomography (CT) scans or magnetic resonance imaging (MRI) performed at baseline and after every three cycles.
|Study Start Date:||January 2005|
|Study Completion Date:||July 2009|
|Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
Experimental: RAD001 plus Depot Octreotide
RAD001 at 5 or 10 milligrams orally once a day plus Octreotide Depot 30 milligrams intramuscularly once every 28 days.
Starting dose of 5 or 10 mg by mouth daily.
Other Name: EverolimusDrug: Octreotide Depot
30 mg injection into the muscle of either buttock once every 28 (±7) days.
RAD001 is a new drug that is designed to block a protein that is important in the growth of cancer cells. Octreotide Depot is FDA approved for the treatment of carcinoid syndrome and hormonal symptoms from certain islet cell carcinomas. Octreotide Depot may also help to block certain proteins that are important in tumor growth.
Before you can start treatment on the study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will be asked questions about your medical history and about any medications you are currently taking or have taken in the past. You will have a complete physical exam and your heart rate, temperature, breathing rate, blood pressure, height, and weight will be measured. You will be asked about your ability to perform every day activities. Blood (about 2 teaspoons) will be collected for routine tests. You will have an electrocardiogram (ECG - a test that measures the electrical activity of the heart) and scans (either Computed Tomography/CT or Magnetic Resonance Imaging/MRI) to evaluate the cancer. Women who are able to have children must have a negative blood pregnancy test.
If the screening evaluations show you are eligible to take part in the study, you may begin treatment. You will take RAD001 by mouth once a day, every day while on study. You should take it in a fasting state or after no more than a light, fat-free meal. You should take RAD001 about the same time each day. Octreotide Depot will be given as an injection into the muscle of either buttock once every 4 weeks while on study. This will be done at M. D. Anderson. Four weeks (28 days) is called one course of treatment.
Clinic visits will occur every 2 weeks during the first 4 weeks and every 4 weeks from then on. At each clinic visit, you will be asked questions about your medical history and about any medications you are currently taking or have taken in the past. You will have a complete physical exam and your heart rate, temperature, breathing rate, blood pressure, height, and weight will be measured. You will be asked about your ability to perform every day activities. Blood samples (about 1 teaspoons) for routine tests will be collected every 2 weeks for the first 8 weeks. After that, blood samples (about 2 teaspoons) will be collected every 4 weeks. CT or MRI scan(s) will be performed every 12 weeks.
If a sample of your tumor tissue that was removed previously is available, it will be analyzed for expression of proteins that may effect tumor growth. However, if a sample is not available, you will not be asked to undergo a biopsy to collect this tissue. This sample may analyzed at any time during the study.
If you experience severe side effects, treatment may be delayed, stopped, or you may receive smaller doses of RAD001 and/or Octreotide Depot. You may continue to receive up to at least 12 courses of study treatment unless the disease gets worse, you decide not to take part any longer, or your doctor decides it is in your best interest to stop treatment. It may be possible to continue treatment beyond 12 courses if you are benefitting from this treatment.
When you stop study treatment, you will be asked to have some tests and evaluations done. About 4 teaspoons of blood will be taken for routine lab tests, You will also have a physical exam and CT scan or MRI scan will be done to check the size and location of your disease.
This is an investigational study. RAD001 is investigational and is not commercially available. The drug combination in this study is also investigational. RAD001 is manufactured by Novartis Pharmaceuticals Corporation. About 60 patients will take part in this study. All will be enrolled at M. D. Anderson.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00113360
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||James Yao, M.D.||M.D. Anderson Cancer Center|