Trial Information

An Open-Label Study of the Safety and Efficacy of Atiprimod Treatment for Patients With Advanced Cancer

Atiprimod was shown to slow or stop the growth of several human tumor cell lines in
laboratory studies. Researchers believe it may have the same effect on tumor cells in
patients with advanced cancer.

Before you can start treatment on the study, you will have what are called "screening
tests". These tests will help the doctor decide if you are eligible to take part in the
study. At the screening visit, you will be asked questions about your medical history and
any medications you use. You will be asked questions about your ability to carry out
everyday activities (performance status). You will have a complete physical exam, including
measurement of your vital signs (blood pressure, pulse, breathing rate, and temperature),
routine blood (about 1 teaspoon) and urine tests, and an electrocardiogram (ECG--a test to
measure the electrical activity of the heart).

You will have a neurological exam, which will include a series of questions and tasks (such
as walking, talking, and touching your nose). The interview will take about 20 minutes to
complete. Additionally, the study doctor will test your reflexes by tapping your arms,
knees, and the bottom of your feet with a rubber triangle-shaped end of a special instrument
that looks like a little hammer. The study doctor will also test your ability to sense
light touch and pinprick, and will check your eyes with a special light source
(ophthalmoscope). You will be asked questions about your physical, social/family,
emotional, and functional well-being, as well as additional concerns you may have regarding
numbness, tingling, discomforts, and difficulties you may be having. The interview will
take about 10 minutes to complete.

The tumor will be measured by tests that are normally used to check the extent of disease in
patients with the same type of cancer. This may include x-rays, MRIs, CT scans, or bone
marrow biopsies. To collect a bone marrow biopsy, an area of the hip or chest bone is
numbed with anesthetic and a small amount of bone marrow and bone is withdrawn through a
large needle. Women who are able to have children must also have a negative pregnancy test
in order to participate in this study.

If you complete all of the screening tests and are eligible to participate in the study, you
will be scheduled to return to the clinic within 14 days, for baseline testing and the start
of treatment (Day 1). You will be asked questions about your medical history and the
medications you used since the last visit. You will have a physical exam, including
measurement of your vital signs, and routine blood tests (about 1 teaspoon). A blood sample
(roughly less than half of a teaspoon) will also be drawn for pharmacokinetic (PK) testing.
PK testing is used to measure the amount of atiprimod in your blood. This first blood
sample will be your "baseline" PK sample, and the drug level in later blood samples will be
compared to it.

You will be assigned to one of 8 specific dose levels of atiprimod, based on when you
entered the study; however, your dose level may be lowered if you experience increased blood
levels of AST and ALT (liver function tests used to monitor for possible liver
inflammation). Your assigned dose level will decide how many tablets or capsules of
atiprimod you will take for each dose. The first group of 3 patients will receive atiprimod
tablets at the lowest dose level for 14 days, followed by 14 days off drug. If no serious
side effects occur, the next 3 patients will receive atiprimod capsules at the lowest dose
level. If no serious side effects occur, the next 3 patients will receive atiprimod
capsules at the next higher dose level and capsules will be used for the rest of the study
(tablets will only be used for the first group of 3 patients). If 1 of the 3 patients
experiences a serious side effect, the next 3 patients will be given the same dose (rather
than the next higher dose) to further evaluate safety at that dose. If no serious side
effects occur, the next 3 patients will receive the next higher dose. Each new dose level
will be tested in this way, until the highest dose level (8th dose level) is reached or
until serious side effects occur, in which case the dose will not be raised any higher.

During the study, you will take your dose of atiprimod orally (by mouth) in tablet or
capsule form once a day for 14 days, followed by 14 days with no atiprimod treatment. These
28 days (4 weeks) will make up one treatment "cycle." If you do not experience a serious
side effect that forces your doctor to remove you from study, and your cancer is stable or
shrinking after 2 months of treatment, you will be eligible to continue on atiprimod
treatment for up to 1 year (a total of 12 cycles). If you experience increased blood levels
of AST and ALT, and these levels return to normal within 7 days of completing the treatment
cycles, you may be eligible to continue atiprimod treatment, but at a lower dose level and
on a modified schedule (atiprimod once a day for 7 days, followed by 7 days off atiprimod).
You should take the atiprimod in the morning at about the same time each day. You should not
eat food for at least 2 hours before and 2 hours after taking atiprimod. You should drink 1
- 2 glasses of water (preferred) or orange juice, soda, tea, or coffee during the 2 hours
before and 2 hours after taking your daily dose of atiprimod, and you may drink water
(preferred) or orange juice, soda, tea, or coffee during the 2-hour period after taking your
daily dose of atiprimod.

After your baseline testing, you will be given your first dose of atiprimod. During the
first 8 hours after your first dose of atiprimod, you will be watched for any side effects
that might occur. You will have several blood samples taken during this period for PK
testing. About a quarter of a teaspoon of blood will be drawn 30 minutes after your first
dose, then again at 60 minutes, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours, and 8 hours
after your first dose, for a total of 2 teaspoons of blood drawn. After these blood
collections, you will go home. You will be given a study diary for recording any other
medications you take and how much you take, as well as any side effects that you experience.
You will also be asked to record the type and amount of beverage consumed during the 2-hour
period before taking atiprimod and the 2-hour period after taking atiprimod. You will be
required to keep this diary up to date during your entire participation on study, and you
must bring it to every study visit.

You will return to the clinic 24, 48, and 72 hours after your first dose (Study Days 2, 3,
and 4). You will be asked questions about your medical history and the medications you used
since the last visit. You will have a physical exam, including measurement of your vital
signs, routine blood (about 1 teaspoon), and an ECG. The ECG will only be done on Day 2
(not on Days 3 and 4). A blood sample (less than half of a teaspoon) will be drawn for PK
testing. You will be given your daily dose of atiprimod.

Before you leave the clinic on Study Day 4, you will be given enough atiprimod to last until
the next visit (in other words, through Study Day 6). You will be instructed to not eat
food for at least 2 hours before or 2 hours after taking atiprimod, and to take the
atiprimod in the morning at the same time each day. You will also be instructed to drink 1
- 2 glasses of water (preferred) or orange juice, soda, tea, or coffee during the 2 hours
before and 2 hours after taking your daily dose of atiprimod. You will be given a diary for
recording when you take the atiprimod, the type and amount of beverage consumed during the
2-hour period before taking atiprimod and the 2-hour period after taking atiprimod, other
medications that you take, and any side effects that you experience.

You will be asked to return to the clinic for tests once a week during the first cycle of
treatment (Days 7, 14, 21, and 28). You will take the atiprimod doses on Days 5-14 at home
as instructed, except for the 2 days during this period that you are scheduled to return to
the clinic (Study Days 7 and 14). These 2 doses will be given to you at the clinic. Before
you leave the clinic on Study Day 7, you will be given enough atiprimod to last until the
next visit (Study Day 14).

During these first four weekly visits (Study Days 7, 14, 21, and 28), you will have several
tests performed. During each visit, you will be asked questions about your medical history
and the medications you used since the last visit. You will be asked questions about the
doses of atiprimod you have taken on your own (number of tablets or capsules taken at each
dose, time each dose was taken, if you ate food or drank something other than water, orange
juice, soda, tea, or coffee during the 2 hours before or after taking study drug, and the
number of glasses of water, orange juice, soda, tea, or coffee that you drank during this
4-hour period). You will have a physical exam, including measurement of your vital signs,
routine blood (about 1 teaspoon) and urine tests. You will have an ECG at Day 28 only (not
on Days 7, 14, or 21). You will also have a neurological exam. You will be asked questions
about your physical, social/family, emotional, and functional well-being, as well as
additional concerns you may have regarding numbness, tingling, discomforts, and difficulties
you may be having.

You will have several PK blood samples taken at your Day 14 visit. About a quarter of a
teaspoon will be taken 30 minutes after you take the atiprimod dose at your Day 14 visit,
and then again at 60 minutes, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours, and 8 hours
after that same dose, for a total of 2 teaspoons of blood drawn. You will also be
instructed to return to the clinic 24, 48, and 72 hours after your Day 14 visit for a single
blood collection. Less than a quarter of a teaspoon of blood will be collected at each of
these 3 visits. A single blood collection (about half of a teaspoon) will also be taken at
your Day 7, Day 21 and Day 28 visits for PK testing.

At your Day 28 visit, you will also have the size of the tumor measured using x-rays, MRIs,
or CT scans, as before. Women who are able to have children will have a blood pregnancy
test.

After the first cycle, you will return to the clinic for evaluation once a month at the end
of each cycle that you are eligible for treatment. If you do not experience a serious side
effect that forces your doctor to remove you from study, and your cancer is stable or
shrinking after 2 months of treatment, you will be eligible to continue on atiprimod
treatment for up to 1 year (a total of 12 cycles).

At each monthly study visit, you will be given enough atiprimod to last until your next
clinic visit (Week 4 of next cycle). You will be given a diary for recording when you take
the atiprimod, the type and amount of beverage consumed during the 2-hour period before
taking atiprimod and the 2-hour period after taking atiprimod, other medications that you
take, and any side effects that you experience. During these monthly visits, you will have
several tests performed. You will be asked questions about the doses of atiprimod you have
taken on your own. You will have a physical exam, including measurement of your vital signs,
routine blood (about 1 teaspoon) and urine tests, and an ECG. You will have a neurological
exam. You will be asked questions about your physical, social/family, emotional, and
functional well-being, as well as additional concerns you may have regarding numbness,
tingling, discomforts, and difficulties you may be having. A single blood collection (less
than half of a teaspoon) will be taken for PK testing. Your tumor will be measured using
the same kinds of scans as before. Women who are able to have children will have a blood
pregnancy test.

If you experience increased blood levels of AST and ALT, and these levels return to normal
within 7 days of completing the treatment cycle, you may be eligible to continue atiprimod
treatment, but at a lower dose level and on a modified schedule. If you do receive a
modified schedule of atiprimod, you will return to the clinic for an additional evaluation
on Week 2 (Day 14) of the modified cycle (in addition to the evaluation that you will have
at the end of the cycle). This evaluation will include the same tests done at the monthly
visits, except that your tumor will not be measured and you will not have a pregnancy test.

Extra visits, tests, and/or procedures may be done at any time during this research study,
if the doctor thinks they are in your best interest.

You will be taken off study if the disease progresses, intolerable side effects occur, or
you do not follow study guidelines for participation.

One month after your last treatment cycle, you will return to the clinic for a follow-up
evaluation. You will be asked questions about your ability to carry out everyday activities
(performance status). You will be asked questions about your medical history and the
medications you used since the last visit. You will have a physical exam, including
measurement of your vital signs, routine blood (about 1 teaspoon) and urine tests, and an
ECG. You will have a neurological exam. You will be asked questions about your physical,
social/family, emotional, and functional well-being, as well as additional concerns you may
have regarding numbness, tingling, discomforts, and difficulties you may be having. A
single blood collection (less than half of a teaspoon) will be taken for PK testing. Women
who are able to have children will have a blood pregnancy test.

This is an investigational study. Atiprimod is authorized by the FDA for research only.
About 61 individuals will take part in this study. All will be enrolled at UTMDACC.