A Phase I Trial of Doxil, Bevacizumab and Temsirolimus

Trial Information

A Phase I Trial of Doxil, Bevacizumab and Temsirolimus

The Study Drugs Liposomal doxorubicin is designed to cause cancer cells to be fragile, which
may cause the cancer cells to die.

Bevacizumab is designed to block or slow down the growth of cancer cells by blocking the
growth of blood vessels that supply nutrients for tumor growth.

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

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a fixed
dose level of liposomal doxorubicin, bevacizumab, and temsirolimus combined, based on when
you joined this study. Up to 9 dose levels of the study drug combination will be tested.
Three (3) participants will be enrolled at each dose level. The first group of participants
will receive the lowest dose level. 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 the study drug combination is found.

Study Drug Administration:

Liposomal doxorubicin, bevacizumab, and temsirolimus will be given in "cycles." Cycles will
be about 21 days (or longer, depending on any side effects you may experience).

Liposomal doxorubicin is given by vein on Day 1 of each cycle. On Day 1 of Cycle 1, you
will receive it over 3 hours. If you tolerate it well in Cycle 1, you will receive it over
60 minutes in Cycle 2. If you tolerate it well in Cycle 2, you will receive it over 60
minutes for all further cycles.

Bevacizumab is given by vein on Day 1 of each cycle. On Day 1 of Cycle 1, you will receive
it over 90 minutes. If you tolerate it well in Cycle 1, you will receive it over 60 minutes
in Cycle 2. If you tolerate it well in Cycle 2, you will receive it over 30 minutes in
Cycle 3. It will continue to be given over 30 minutes in Cycle 4 and further cycles, as
long as you still tolerate it well.

Temsirolimus is given by vein on Days 1, 8, and 15 of each cycle. 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.

Because of a nationwide shortage of liposomal doxorubicin, you may only receive temsirolimus
and bevacizumab until liposomal doxorubicin becomes available.

Study Visits:

During Cycle 1, you will have a physical exam once and blood will be drawn weekly (about 1
tablespoon) for routine tests.

For Cycle 2 and further cycles, you will have a physical exam and blood drawn (about 1
tablespoon) for routine tests once every 3 weeks.

The status of the disease will be checked by a CT or MRI scan after every 2 cycles, for
Cycles 2-6, then every 2-3 cycles.

Additional Procedures for Some Participants:

If you are in the group that receives the highest safe dose of the study drugs, you will
have the following additional procedures performed:

- You will have a biopsy performed at the end of Cycle 1. The biopsy will be used for
research to see how the study drug combination acts in the body and to learn how it may
affect cancer cells.

- You will have a DCE-MRI scan at 24-48 hours after your first study drug infusion (Cycle
1), and at the end of Cycle 1. These DCE-MRI scans will be used for research to see
how the study drug combination is affecting blood vessels that supply nutrients and
oxygen to tumor cells.

Length of Study Participation:

You may continue to receive additional cycles of the study drugs, unless the cancer goes
away completely, gets worse, or if intolerable side effects occur. In that case, you will
be taken off study.

Long-Term Follow-Up:

After your last dose of the study drug, you will receive up to 3 phone calls from the study
staff. The calls will be 1 month apart, and you will be asked how you are doing.

This is an investigational study. Liposomal doxorubicin, bevacizumab, and temsirolimus are
commercially available. Liposomal doxorubicin is FDA approved for the treatment of multiple
myeloma, ovarian cancer that has returned, and Kaposi's sarcoma. 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.

The combination of liposomal doxorubicin, bevacizumab, and temsirolimus is not FDA approved.
At this time, it is only being used in research.

Up to 206 patients will take part in this study. All will be enrolled at MD Anderson.