IRB Number:

07-006088

Trial Status:

Open for Enrollment

Phase: II

Why is this study being done?

Patients are being asked to take part in this research study because they have been diagnosed with advanced cancer.

The Purpose of the study is:
- To determine the highest tolerated dose of a new investigational drug called BMS-753493 in patients with advanced cancer.
- Evaluate the effect (good or bad) and the safety of the drug, and measure the levels of the drug in the blood at various times throughout the study.
- Look at the effect of drug on certain cancers (ovarian, renal and breast).

BMS-753493 is a drug that has two parts that work together to get rid of the patient's cancer. The first part, called "folate" guides the drug to the cancer cells. The second part of the drug, called "epothilone", is the part of the drug that is designed to kills the cancer cells. Studies in animals and humans have shown that some cancer cells express the folate receptor on their surface. This means that the folate can find these cells and then guide the epothilone to these unhealthy cells to do its work. This will hopefully reduce side effects by keeping the epothilone away from healthy cells that do not contain the folate receptors.

Who is Eligible to Participate in the Study?

- Age 18 or older
-Diagnosed with advanced cancer

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

To ensure the patient's safety and to determine if they are eligible for the study, the doctor and study team will look through the patient's medical chart, ask the patient questions, and begin scheduling tests and procedures. This is called the screening period. If the study doctor determines that the patient does not meet the criteria for safe drug administration, they will not be allowed to take part in this study. If the patient is not eligible, their doctor will discuss other treatment options with the patient. The screening period is about 28 days long; it can be less based on when the patient's tests are performed.

If agreeing to be in the study, patients will be asked to participate in the following:

During the Screening Period the following tests and procedures will be done:
- Medical history, physical examination and neurological examination.
- ECOG Performance status (questions about how well the patient performs theer every day activities).
- Temperature, heart rate, breathing rate, blood pressure (vital signs), height and weight.
- Electrocardiogram (A painless test of the electrical action of the heart).
-Echocardiogram (A painless measurement of the patient's heart's function and structure. An echocardiogram is an ultrasound of the patient's heart.

- Assessment of the patient's cancer:
* This can be done by an x-ray machine that makes computerized pictures of the inside of the patient's body (this is called CT/CAT scan), the use of magnetic waves
to take pictures of the inside of the patient's body (this is called MRI) or if the patient's cancer is located on the skin, the study doctor will look at the patient's skin and take pictures and measurements of their cancer.
* If the patient has non-measurable, confirmed, advanced ovarian cancer, the doctor will do a blood test called CA125 and collect about 1 tablespoon of blood.

- Pulmonary Function Tests (PFTs) to measure any lung abnormalities. These tests include:
* Spirometry: patients will breath into a machine called a spirometer to measure how much and how fast air moves out of their lungs
* Lung diffusing capacity test (DLCO): patients will breathe in a mixture of air and gas such as helium (about 10 percent) and carbon monoxide (about 3000 parts per
million, a level which is considered safe), hold their breath for 10 seconds, then breath out into a collection system. This will measure how efficiently the lungs transfer oxygen from the air into the bloodstream.

- Blood and urine tests:
* Routine blood (approximately 1 to 2 tablespoons) and urine tests

Investigational Tests and Procedures that will be performed during the Screening period:
Non-routine blood tests, including Serum Folate and homocysteine levels, thyroid function tests, and for Troponin to measure how the patient's heart is working.
- In women of child bearing potential, (if they can have children) a blood test for pregnancy (about 1 teaspoon) will be required before starting treatment.
- Archived or New Tumor Sample (not optional) The study Sponsor also requires the study doctor to send a sample of the patient's cancer cells (collected in the past) to a central vendor for examination of how many folate receptors are on the patient's tumor cells.

- Blood tests:
* Test that checks for folate receptor and folate receptor antibodies

Some of these tests and procedures need to be done near the date of the patient's first dose of drug. If they were done too long ago they may need to be repeated. The doctor/study team will discuss this with the patient. The doctor/study team will let the patient know if the results of their blood tests and procedures meet the criteria for the patient to enter the study. If they do, and you still want to take part, the patient will be enrolled in the study and will begin the treatment period.

If taking part in this research study patients will be given BMS-753493.
The dose of BMS-753493 that can safely be given is not known. To find this out and to minimize the risk to any individual taking part, the procedure below will be followed:
- Between three and six individuals will be assigned to a low dose level of BMS-753493 and will be watched closely. For the first three patients, there will be a world-wide one week waiting period between each individual to make sure it is safe for the next individual to receive BMS-753493.
- Once the first BMS-753493 dose level is known to be safe, another 3-6 patients will be assigned to the next higher BMS-753493 dose level and will be watched closely for
side effects.
- This will continue until the highest dose of BMS-753493 that can safely be given is known.

Once the highest dose of BMS-690514 that is tolerable is selected, 12 subjects will be treated at this dose level.

BMS-753493 will be administered as a 3 to 5 minute infusion through the patient's vein on Days 1, 2, 3, and 4 of every 21-day cycle. It is not known at this time whether BMS-753493 will have any effect on the patient's cancer. Therefore, the patient may receive no benefit from their participation in this study.

If the patient is tolerating the treatment, that is, not having any significant side effects, and they continue to meet all other study criteria, their treatment will be repeated every 21 Days. If the patient is having significant side effects their doctor may discontinue BMS-753493 treatment completely or reduce the dose level given to the patient.

During the Treatment Period the following tests and procedures will be done:
- Physical examination as well as a review of any medications the patient may have taken and any side effects they may have experienced.
- Neurological examination
- Vital signs before and after the patient takes BMS-753493.
- Weight
- Routine urine tests
- Blood tests: Approximately 9 tablespoons total will drawn from the patient during the study. This volume will not be drawn all at once, but rather will be spread out at various points over a period of one to two months. Each individual blood draw will consist of approximately 1/2 tablespoons blood.
- Routine blood tests will be collected.
- If patient is a female of child-bearing potential (if they can have children), the patient will also have a pregnancy test every cycle.
- Non-routine blood tests, including thyroid function tests, homocysteine and serum folate levels.

To determine the amount of BMS-753493 in the patient's body (pharmacokinetic or PK), blood samples and urine will be collected at different time points during
the course of the study. PK blood samples are only collected in the first 22 days of the study.
- Electrocardiograms at the same Timepoints of the PK blood collection.
-CT or MRI Tumor assessments (every odd cycle) or CA125 blood tests for patients with non-measurable, confirmed, advanced ovarian cancer (day 1 of every Cycle).
-Echocardiogram every fourth cycle.

If the patient experiences any of the following side affects during the study, their treatment may end:
- unacceptable side effects,
- their cancer gets worse,
- patient becomes pregnant,
- their doctor thinks it is in the patient's best interest to stop,
- the study closes, or
- Patient no longer wants to take part.

Once the patient's treatment ends (on the last day of treatment, or when taken off study) the following tests and procedures will be done:
- Physical examination, including physical measurements, as well as a review of any medications the patient may have taken and any side effects they may have experienced.
- Neurological Exam
- Vital signs
- ECOG performance status (Questions about how well the patient performs their every day activities).
- 12-lead ECG.
- Blood and urine tests:
* Routine blood (about 1-2 tablespoons) and urine tests.
* Non-routine blood tests, including thyroid function tests, serum folate and homocysteine.
* If patient is a woman of child bearing potential (if they can have children) a pregnancy test (about 1 teaspoon) will be performed.
- CT or MRI Tumor assessments (every odd cycle) or CA125 blood tests for some patients with non-measurable, confirmed, advanced ovarian cancer (day 1 of every
Cycle).
- Pulmonary Function Tests.
- Echocardiogram

Patients will need to see the study doctor for a follow-up visit about 30 days after their study ends. If the patient experiences any side effects after the 30 days they will need to continue seeing the study doctor until the side effects have resolved or the study doctor tells the patient that it is no longer necessary for the patient to see him/her.

If agreeing to take part in this study, patients will be asked to participate in all the required procedures and visits to the best of their ability. Patients will be expected to do the following:
- Keep all appointments and follow instructions given by the study doctor/study team.
- Do not take any other treatments for their cancer (chemotherapy, radiation, hormones, alternative therapies such as herbs, etc.).
- Patients may not take multi-vitamins, supplements and folic acid at anytime during the study.

How long will the Study run?

The length of time the patient will be in this study will depend on the response of their cancer to the drug and how well they tolerate the treatment. Patients may continue in the study as long as the patient and their doctor feel the patient is benefiting, tolerating the drug well and their disease is not worsening. The patient may be taken off of the study if the disease gets worse or if they experience bad side effects.

Sponsor(s): Bristol-Myers Squibb

Study Activation/Registration Date: 12/11/2007

IRB Review and Approval Date: 11/28/2007

Study Type: Dosing/Treatment

Projected Accrual: The plan is to have up to 71 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Lynn C. Hartmann, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 06/18/2008