Phase I Trial of Bevacizumab and Temsirolimus in Combination With 1) Carboplatin, 2) Paclitaxel, 3) Sorafenib for the Treatment of Advanced Cancer

Advanced Cancer Clinical Trial

Official title: Phase I Trial of Bevacizumab and Temsirolimus in Combination With 1) Carboplatin, 2) Paclitaxel, 3) Sorafenib for the Treatment of Advanced Cancer

Status Active, not recruiting

Clinical Trial Summary

The goal of this clinical research study is to find the highest tolerable dose of the combination of bevacizumab (Avastin) and temsirolimus (Torisel) that can be given with 1 of 3 other study drugs --carboplatin (Paraplatin), paclitaxel (Taxol), or sorafenib (Nexavar). The safety of these drug combinations will also be studied.

Clinical Trial Description

The Study Drugs:

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.

Temsirolimus is designed to block the growth of cancer cells, which may eventually cause the cancer cells to die.

Carboplatin is designed to damage the DNA (the genetic material of cells)of cancer cells, which may will eventually cause the cancer cells to die.

Paclitaxel is designed to damage the DNA of cancer cells, which may eventually cause the cancer cells to die.

Sorafenib is designed to block the function of important proteins in cancer cells. These proteins, when active, are in part responsible for the abnormal growth and behavior of cancer cells.

Study Drug Dose Level:

If you are found to be eligible to take part in this study, your doctor will decide which study drugs you will receive based on the disease type and on the drugs you have taken in the past.

Every participant will receive bevacizumab and temsirolimus. The study staff will tell you which of the other 3 drugs (carboplatin, paclitaxel, or sorafenib) you will receive.

Once it is decided which drugs you will receive, you will be assigned to a dose level of the drug combination based on when you join this study. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants on each drug combination will receive the lowest doses. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of each dose combination is found.

Your dose of study drugs may be lowered later, if you do not tolerate the study drug combination well.

Once the highest tolerated dose is found for each group, up to 10 more participants will be added to each group at that dose level. This is called an extension group.

Study Drug Administration:

Each cycle is about 21 days or 28 days, depending on which study drug combination you receive.If you experience side effects, the start of the next cycle may be delayed. Your doctor will tell you on which dose level you will be assigned.

SORAFENIB ARM:

If you are assigned to take sorafenib, you will take it by mouth 1 or 2 times every day (the study staff will tell you how often to take it). You should take sorafenib on an empty stomach, either 1 hour before a meal or 2 hours after a meal.

On Day 1 of each cycle, you will receive bevacizumab by vein. The first infusion is over 90 minutes. The next infusion may be over 60 minutes if the first infusion was well-tolerated. If you tolerate the second infusion well, the third infusion may be over 30 minutes.

On Days 1, 8, and 15 of each cycle, you will receive temsirolimus by vein. During Day 1 of Cycle 1, you will receive it over 60 minutes. If you tolerate it well on Day 1 of Cycle 1, it will be given over 30 minutes on Days 8 and 15 of Cycle 1 and over 30 minutes in further cycles, as long you still tolerate it well.

CARBOPLATIN ARM:

If you are assigned to take carboplatin,you will receive it by vein over 1 hour on Day 1 of each cycle.

On Day 1 of each cycle, you will receive bevacizumab by vein. The first infusion is over 90 minutes. The next infusion may be over 60 minutes if the first infusion was well-tolerated. If you tolerate the second infusion well, the third infusion may be over 30 minutes.

On Days 1, 8, and 15 of each cycle, you will receive temsirolimus by vein. During Day 1 of Cycle 1, you will receive it over 60 minutes. If you tolerate it well on Day 1 of Cycle 1, it will be given over 30 minutes on Days 8 and 15 of Cycle 1 and over 30 minutes in further cycles, as long you still tolerate it well.

PACLITAXEL ARM DOSE LEVELS 1-8:

If you are assigned to take paclitaxel on Dose Levels 1 - 8, you will receive it by vein over 3 hours on Days 1, 8, and 15 of each cycle.

On Day 1 of each cycle, you will receive bevacizumab by vein. The first infusion is over 90 minutes. The next infusion may be over 60 minutes if the first infusion was well-tolerated. If you tolerate the second infusion well, the third infusion may be over 30 minutes.

On Days 1, 8, and 15 of each cycle, you will receive temsirolimus by vein. During Day 1 of Cycle 1, you will receive it over 60 minutes. If you tolerate it well on Day 1 of Cycle 1, it will be given over 30 minutes on Days 8 and 15 of Cycle 1 and over 30 minutes in further cycles, as long you still tolerate it well.

PACLITAXEL ARM DOSE LEVELS 9 - 13:

If you are assigned to take paclitaxel on Dose Levels 9 - 13, you will receive paclitaxel by vein over 3 hours on Days 1, 8, and 15 of each cycle.

On Days 1 and 15 of each cycle, you will receive bevacizumab by vein. The first infusion is over 90 minutes. The next infusion may be over 60 minutes if the first infusion was well-tolerated. If you tolerate the second infusion well, the third infusion may be over 30 minutes.

On Days 1, 8, 15, and 22 of each cycle, you will receive temsirolimus by vein. During Day 1 of Cycle 1, you will receive it over 60 minutes. If you tolerate it well on Day 1 of Cycle 1, it will be given over 30 minutes on Days 8, 15, and 22 of Cycle 1 and over 30 minutes in further cycles, as long you still tolerate it well.

Study Visits:

During Cycle 1:

• Urine will be collected for routine tests on Day 1.

• You will have a physical exam, including measurement of your weight and vital signs (blood pressure, breathing rate, heart rate, and temperature).

• You will be asked how well you are able to perform the normal activities of daily living (performance status) on Days 1 and 8.

• Blood (about 1 tablespoon) will be drawn for routine tests on Days 1, 8, and 15.

On Day 1 of Cycles 2 and beyond:

• You will have a physical exam, including of your weight and vital signs..

• Your performance status will be recorded.

• Blood (about 1 tablespoon) and urine will be collected for routine tests

After Cycle 2, you will have a CT scan or MRI scan to check the status of the disease every 2-3 cycles. After 6 months, this may be performed up to every 4 cycles if the doctor thinks it is in your best interest.

Length of Study:

You may remain on study for as long as the doctor thinks it is in you best interest. You will be taken off study if the disease gets worse or intolerable side effects occur.

This is an investigational study. Bevacizumab, temsirolimus, carboplatin, paclitaxel, and sorafenib are all commercially available. Bevacizumab is FDA approved for the treatment of colorectal cancer and a type of lung cancer. Temsirolimus is FDA approved for the treatment of kidney cancer that has spread. Carboplatin is FDA approved for the treatment of ovarian cancer or non-small cell lung cancer. Paclitaxel is FDA approved for ovarian, breast cancer, and AIDS-related Kaposi's sarcoma. It is also approved in combination with cisplatin for the treatment of ovarian and non-small cell lung cancer. Sorafenib is FDA approved for the treatment of kidney cancer.

The use of these drugs together is investigational.

Up to 278 patients will take part in this study. All will be enrolled at MD Anderson. ;

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

• NCT number: NCT01187199
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 19, 2010
• Completion date: April 30, 2026