Clinical trial NCT00607113
Conditions: Neuroendocrine Carcinoma
Keywords: Neuroendocrine Carcinoma Avastin Bevacizumab RAD001 Everolimus
Sponsor: M.D. Anderson Cancer Center
Start date: 2008-01-01; Completion date: 2011-10-01
Enrollment: 41 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Primary Objectives:

* To determine the effect of Avastin on tumor blood flow as determined by functional computed tomography (CT) in patients with low or intermediate grade neuroendocrine carcinoma.
* To determine the effect of RAD001 on tumor blood flow as determined by functional CT in patients with low or intermediate grade neuroendocrine carcinoma.
* To determine the effect of adding the second agent (Avastin or RAD001) to the first agent (RAD001 or Avastin) on tumor blood flow as determined by functional CT

Secondary Objectives:

* To determine the clinical activity (objective response rate and progression free survival duration) of Avastin and RAD001 in patients with low or intermediate grade neuroendocrine carcinoma.
* To determine the biochemical response rate of Avastin and RAD001 in patients with low or intermediate grade neuroendocrine carcinoma.
* To determine the safety and tolerability of Avastin and RAD001 in patients with low or intermediate grade neuroendocrine carcinoma.

Detailed description:
The Study Drugs:

Avastin is designed to prevent the formation of new blood vessels that help cancer cells to grow. RAD001 is designed to block a protein that is important in the growth of cancer cells.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. During Cycle 1, one group will receive Avastin and the other group will receive RAD001. Each study cycle is 3 weeks long. In Cycle 2 and every cycle after that, participants in both groups will receive both study drugs. There is an equal chance of being assigned to either group.

RAD001 Administration:

RAD001 tablets are taken once a day by mouth, followed by a large glass of water. The tablets are in a blister-pack under aluminum foil. The blisters should only be opened at the time you take the study drug.

You may either take RAD001 on an empty stomach or after a low-fat meal. Some examples of low-fat meals include: cereal with fat-free milk, muffin or bagel with fat-free spread, or fruit salad. You should avoid taking RAD001 after large fatty meals because this will lower the amount of RAD001 your body absorbs. Your dietary habits around the time you take RAD001 should be as consistent as possible throughout the study.

You should take RAD001 at about the same time each day. The study staff will give you a medication diary that you should bring to every study visit. You will be asked to use the diary by writing down the date and time you take RAD001, how many tablets you take, and any side effects you may experience.

Avastin Administration:

Avastin is given through a needle in a vein in the arm. The first dose will be given over about 90 minutes. If no intolerable side effects occur, the second dose will be given over about 60 minutes, and if again no intolerable side effects occur, each dose after that will be given over about 30 minutes.

Other Medications:

If you experience side effects from an Avastin infusion (such as fever/chills), you may receive additional medicine(s) at that time and before each later Avastin dose, in order to decrease the risk of side effects.

Study Visits:

On Day 1 of Cycle 1, you will receive your assigned study drug.

At the beginning of Cycle 2 and every cycle after that, you will be asked about any side effects you are experiencing. You will have a complete physical exam performed, including measurement of your vital signs and weight. Blood (about 3 teaspoons) and urine will also be collected for routine tests.

On Day 8 of Cycles 1 and 2 only, about 2 teaspoons of blood will be drawn for routine tests. These blood draws may be done at a local lab closer to your home.

Every 9 weeks, to check the status of the disease, you will have either CT scans or MRI scans of the tumor(s). The scans will be the same type that you had performed during screening. You will also have additional blood drawn (about 1-2 tablespoons each time) to check any tumor markers that were found to be increased in your blood during the screening tests.

In order to learn about the flow of blood to the tumor, non-routine functional CT scans will be performed at the end of Cycles 1 and 3. When possible, these scans will be performed at the same times as the routine CT scans.

Length of Study Treatment:

You may receive up to 12 cycles of study treatment, as long as you are benefitting. You will be taken off study early if the disease gets worse or intolerable side effects occur.

This is an investigational study. RAD001 is not commercially available or FDA approved for this type of cancer. Avastin is commercially available and FDA approved for the treatment of advanced cancer of the colon and rectum. At this time, this drug combination is being used for research only.

Up to 36 patients will be enrolled in this study. All will be enrolled at The University of Texas (UT) MD Anderson Cancer Center.

Arms: arm 1: Cycle 1 (First 3 weeks of study) - Avastin 15 mg/kg intravenous (IV) arm 2: Cycle 2: Avastin 15 mg/kg intravenous (IV) every 3 weeks + RAD001 10 mg orally daily for 3 weeks arm 3: Cycle 1 (First 3 weeks of study)- RAD001 10 mg orally daily for 21 Days
Interventions: intervention 1: Avastin intervention 2: RAD001
Intervention descriptions: intervention 1: 15 mg/kg By Vein Over 90 Minutes Every 21 Days intervention 2: 10 mg By Mouth Daily For 21 Days

Protocol documents: