Study of Nano-Curcumin and Resveratrol

The Study Drugs:

Curcumin is the active ingredient in the spice, turmeric. It is a natural anti-inflammatory
compound and has shown anti-tumor activity. Nano-curcumin is designed to be better absorbed
by the body than regular curcumin.

Resveratrol is a natural anti-inflammatory compound that is used to help protect the heart
and nervous system. It may also have anti-tumor activity.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 3
groups. Arm 1 will take nano-curcumin only. Arm 2 will take resveratrol only. Participants
will enroll in Arm 1 or Arm 2 at the same time. Three (3) to 6 participants will be enrolled
at each dose level of each arm. The first group of participants will receive the lowest dose
level of the study drug. Each new group will receive a higher dose of the study drug than
the group before it, if no intolerable side effects were seen. This will continue until the
highest tolerable dose of the study drug is found. Up to 4 dose levels of nano-curcumin will
be tested in Arm 1. Up to 2 dose levels of resveratrol will be tested in Arm 2. Once the
highest tolerable dose of each arm is found, up to 14 extra participants will be enrolled on
each arm for extra safety testing.

Once the highest tolerable dose of nano-curcumin alone and resveratrol alone are found, Arm
3 will begin enrolling participants who will receive the combination of nano-curcumin and
resveratrol. The first group of participants will receive the lowest dose level of the study
drug combination. Each new group will receive a higher dose of the study drug combination
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. Up to 3 dose levels
of the study drug combination will be tested. Once the highest tolerable dose of the study
drug combination is found, up to 14 extra participants will be enrolled for extra safety
testing.

In some cases, extra participants may be enrolled at dose levels shown to be safe for extra
safety and/or PK and PD testing.

You will be assigned to a dose level of nano-curcumin alone, resveratrol alone, or the study
drug combination (nano-curcumin and resveratrol) based on when you join this study.

The dose of the study drugs that you receive may be lowered if you have any intolerable side
effects. You will not receive any doses of the study drug combination higher than the dose
level that you are first assigned, but you may be re-assigned to another Arm at a dose level
that has been found to be safe.

If the disease gets worse while you are on study and the doctor thinks it is in your best
interest, you may be reassigned to a different Arm.

Study Drug Administration:

Each study "cycle" is 28 days long.

Starting on Day 1 of Cycle 1, you will begin taking nano-curcumin 2 times each day and/or
resveratrol 1 time each day.

If you are in Arm 1 or Arm 3, you will take a single dose of curcumin and/or resveratrol on
Day -3 (3 days before the first dose of study drug[s]) so that blood can be drawn for
pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the blood at
different time points.

Nano-curcumin is a powder that comes in a paper packet, and you will take it by mouth on an
empty stomach with a full glass of water (8 ounces). Resveratrol is a tablet that you will
take by mouth with water. If you are not tolerating the doses and your doctor thinks it is
needed, you may take nano-curcumin and/or resveratrol in divided doses several times a day
with food.

Study Visits:

Every week of Cycle 1 and then as often as the doctor thinks it is needed, blood (about 2
teaspoons) will be drawn for routine tests.

At the end of Cycles 1 and 2, you will complete a questionnaire about your quality of life.
It should take about 5-10 minutes to complete.

Before you begin each cycle:

- Your medical history will be recorded.

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

- Your performance status will be recorded.

- You will be asked about any side effects you may be having.

At the end of Cycle 2 and then every 2-3 cycles:

- You will have a chest x-ray, CT, MRI, and/or PET scan to check the status of the
disease. If the study doctor thinks it is needed, these scan may be performed more
often. You also may have extra types of scans not listed in this consent form.

- If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to measure
tumor markers.

PK Testing for Arms 1 and 3:

If you are in Arm 1 or Arm 3, blood (about ½ teaspoon each time) will be drawn for PK
testing at the following times:

- On Day -3 of Cycle 1, blood will be drawn before the dose and then 6 more times over
the next 6 hours after the dose.

- On Day -2 of Cycle 1, blood will be drawn 1 time.

- On Day 1 of Cycle 1, blood will be drawn before the dose and then 6 more times over the
next 6 hours after the dose.

- On Day 2 of Cycle 1, blood will be drawn 1 time.

PK Testing for Arm 2:

If you are in Arm 2, blood (about ½ teaspoon each time) will be drawn for PK testing at the
following times:

- On Day 1 of Cycle 1, blood will be drawn before the dose and then 6 more times over the
next 6 hours after the dose.

- On Day 2 of Cycle 1, blood will be drawn 1 time.

Length of Study:

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

Your participation on the study will be over once you have completed the end-of-study visit.

End-of-Study Visit:

Within 30 days after your last dose of the study drug(s), you will have an end-of-study
visit. At this visit the following tests and procedures will be performed:

- Your medical history will be recorded.

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

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests.

- You will be asked about any side effects you may be having.

- If the study doctor thinks it is needed, you will have a chest x-ray, CT, MRI, and/or
PET scan to check the status of the disease. If the study doctor thinks it is needed,
you may also have extra types of scans.

- If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to
measure tumor markers.

This is an investigational study. Nano-curcumin is a commercially available substance,
which is commonly used as a food additive. Nano-curcumin is not FDA approved for any usage.
At this time, nano-curcumin is only being used in research. Resveratrol is a commercially
available substance, which is commonly used as a nutritional supplement At this time, the
combination of nano-curcumin and resveratrol is only being used in research.

Up to 96 patients will take part in this study. All will be enrolled at M. D. Anderson.