Trial Information

A Randomized, Placebo-controlled, Blinded Phase II Study of Huachansu & Gemcitabine in Pancreatic Cancer

The Study Drugs:

HuaChanSu is a substance used in China to treat different types of cancer. One of the major
elements of the substance is bufalin, which is an ingredient that has been shown to block
the growth of tumor cells.

Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells
to die.

Screening:

Before you can receive study treatment, you will have "screening tests." These tests will
help the study doctor decide if you are eligible to take part in this study. The following
tests will be performed:

- You will be asked questions about your medical history and any symptoms you may have
now.

- You will have a complete physical exam.

- Your vital signs (temperature, heart rate, breathing rate, and blood pressure), height,
and weight will be measured.

- You will be asked how well you are able to perform the normal activities of daily
living (a performance status evaluation).

- You will have an electrocardiogram (ECG-a test that measures the electrical activity of
the heart).

- To check the status of the cancer, you will have computed tomography (CT) scan(s)
and/or magnetic resonance imaging (MRI) scans of your abdomen, pelvis, and any other
areas where there is disease.

- You will complete a short questionnaire that will ask questions about your quality of
life. This will take about 5 minutes to complete.

- A traditional Chinese medicine diagnosis will also be done. This will include
diagnosis by a study doctor. The doctor will take your pulse (heart rate), look at
your tongue, and ask you a few questions about your health. The doctor will also use a
heart-rate machine and take a photograph of your tongue. This will allow a more
scientific check of your heart rate and tongue condition.

- You will have blood (about 3 teaspoons) collected for routine safety tests. This
routine blood draw will include a pregnancy test for women who are able to have
children. To be eligible to take part in this study, the pregnancy test must be
negative.

- You will have 1 biopsy of your tumor tissue to check your cancer type. To collect a
tumor tissue biopsy, an area where cancer is located is numbed with anesthetic, and a
small amount of tumor tissue is withdrawn through a large needle.

Randomization:

If you are found to be eligible and decide to take part in this study, you may begin
treatment.

The first 3 participants enrolled on this study will be given HuaChanSu and gemcitabine, to
find out if this dose combination can be tolerated. After the first 3 participants are
enrolled, all other participants will be randomly assigned (as in the toss of a coin) to
receive HuaChanSu and gemcitabine or gemcitabine and the placebo. The first 20 participants
have an equal chance of receiving HuaChanSu or placebo, but after that point, participants
will have a better chance of being assigned to the group that is responding better to their
study combination. All participants will receive the same dose level of gemcitabine, but
you will not know if you are given HuaChanSu or placebo. However, this information can be
found out if medically necessary.

Study Treatment:

Before the study drug infusions begin, you will be fitted with a peripherally-inserted
central catheter (PICC) by a specially trained nurse. A PICC is a tube that is inserted
into a vein, either in your arm or under the collarbone, to make it easier to give you
gemcitabine with or without HuaChanSu. This is an outpatient procedure. You will be given a
separate consent form for the insertion of the PICC. It will explain the risks of the
procedure and how to take care of the PICC. Your doses of gemcitabine and either HuaChanSu
or a placebo (a saline [salt water] solution that looks like HuaChanSu but has no effects)
will be given through the PICC while you are on this study.

- HuaChanSu (or placebo) will be given as a 2-hour continuous (nonstop) infusion through
the PICC. You will receive the 2-hour dose 5 days a week (5 days in a row each time)
for 3 weeks. This will be followed by 1 week of not receiving the drug.

- Gemcitabine will be given through a needle in a vein over 30 minutes on Days 1, 8, and
15, followed by 1 week where no study drug is given. Each 4-week treatment period is
called a study "cycle."

PK Testing:

During Cycle 1 only, you will have extra blood (about 1 teaspoon each time) collected at
various time points for pharmacokinetic (PK) testing. PK testing measures the amount of
study drug in the body at different time points. PK blood samples will be drawn 4 times
over a 24-hour period on Day 1 and then once each on Days 7, 14, and 21.

Study Tests:

Before each new cycle, you will be asked questions about your current health, and you will
have a complete physical exam. Your vital signs and weight will be measured. You will have
a performance status evaluation. You will complete a questionnaire about your quality of
life. The questionnaire will take about 5 minutes to complete. You will also have blood
(about 3 teaspoons) drawn for routine safety tests.

On Days 8 and 15 of each cycle, you will also have blood (about 3 teaspoons) drawn for
routine safety tests.

Every 8 weeks (starting in Cycle 3), to check the status of the cancer, you will have CT
and/or MRI scan(s) of your abdomen, pelvis, and any other areas where there is disease.

Length of Study Participation:

You may continue to receive more cycles of treatment, as long as the cancer does not get
worse and intolerable side effects do not occur.

You will be taken off this study if the cancer gets worse, intolerable side effects occur,
new information shows that the treatment is not right for you, you are not able to follow
the study rules, the study is stopped, or you decide to leave the study for any reason. If
you are thinking about leaving the study, please tell your study doctor, so that you may be
told how to end treatment safely as well as what other treatment options are available.

End-of-Treatment Visit:

You will be asked to have a final study visit 4 weeks after your last dose of study drugs.
During this visit, you will have the following tests and procedures performed:

- You will have blood (about 3 teaspoons) drawn for routine safety tests.

- You will be asked questions about your medical history.

- You will have a complete physical exam, and your vital signs and weight will be
measured.

- You will have a performance status evaluation.

- You will complete a questionnaire about your quality of life.

- To check the status of the cancer, you will have computed tomography (CT) scan(s)
and/or magnetic resonance imaging (MRI) scans of your abdomen, pelvis, and any other
areas where there is disease (if these were not performed close to the time that you
stopped study treatment).

This is an investigational study. HuaChanSu is a commercially available medication that is
approved by the Chinese FDA for the treatment of pancreatic cancer. Gemcitabine is approved
by the Chinese FDA for the treatment of pancreatic cancer. In this study, the combination
of these drugs is being used for research only.

Up to 80 patients will take part in this study. All will be enrolled at Fudan University
Cancer Hospital.