Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma

Before possible study participants can receive treatment with imatinib mesylate and
paclitaxel, their tumor tissue that was previously collected (at the surgery to diagnose your
tumor) will be tested for the following three biomarkers: c-Kit, PDGFR-B, and Abl. Those
participants who have at least one positive biomarker will be eligible for treatment on this
study.

Paclitaxel is a chemotherapy drug used in the treatment of ovarian cancer. Imatinib mesylate
is a medication that blocks several proteins that are important in the development of cancer.

Before treatment starts, you will have a complete physical exam, routine blood tests (about
2-3 teaspoons), an electrocardiogram (ECG--a test to measure the electrical activity of the
heart). You will have an echocardiogram (an ultrasound test used to visualize the structures
of the heart), a chest x-ray, and a CT scan or MRI of the abdomen and pelvis. Women who are
able to have children must have a negative blood pregnancy test.

Routine blood tests (about 2 teaspoons) will be done weekly during treatment, and before each
course of therapy, which is every 3 weeks. A complete checkup including evaluation of side
effects, will also be done before each course of therapy and at the end of therapy (3 weeks
after treatment ends).

There are two phases to this study, Phase I and Phase II. If you are assigned to Phase 1, you
will receive treatment with imatinib mesylate and paclitaxel. Phase 1 will study 3 different
doses of imatinib mesylate in combination with a fixed dose of paclitaxel. The Phase I part
of the study will help researchers learn the most effective dose of imatinib mesylate to be
used in combination with paclitaxel. All participants in Phase 1 will receive one of three
doses of imatinib mesylate to be given with a standard dose of paclitaxel. You will be
assigned to a specific dose level based on the number of participants treated at the time of
your enrollment.

The Phase II portion of the study will begin only after the most effective dose of imatinib
mesylate has been determined.

If you are assigned to Phase II, you will be randomly assigned (as in the toss of a coin) to
one of two treatment groups. Participants in one group will receive treatment with paclitaxel
only (every 21 days). Participants in the second group will receive treatment with paclitaxel
(every 21 days) along with imatinib mesylate (every day). The dose level of imatinib mesylate
that you receive will be the same as the dose used during Phase I. The computer-generated
assignment will favor the treatment group which is more effective. For example, if the
combination of paclitaxel and imatinib mesylate is more effective than paclitaxel alone, then
more patients will be selected to receive the combination therapy.

You will receive paclitaxel by vein over 3 hours every 21 days. Those participants who are
assigned treatment with both paclitaxel and imatinib mesylate will begin taking imatinib
mesylate the day after the first dose of paclitaxel. A single dose of imatinib mesylate will
be taken by mouth every day.

Evaluation of tumor response (for participants who already have the disease) will be
determined by CT scan or MRI and chest x-ray (patients with chest disease). These scans will
be taken after Courses 2 and 4 , then after every 3 courses until the therapy is finished,
and once more at the end of therapy. Patients who show no signs of the disease will be given
a total of up to 6 courses. Patients who have the disease may continue treatment until the
disease gets worse. You will be taken off study if the disease gets worse or intolerable side
effects occur. If you are removed from the study, you will be asked to have a follow-up CT
scan or MRI and chest x-ray to evaluate the tumor.

THIS IS AN INVESTIGATIONAL STUDY. Paclitaxel is commercially available and approved for use
in the treatment of ovarian cancer. Gleevec® is also commercially available and approved for
use in the treatment of certain types of adult leukemias and stomach cancers. The combination
of paclitaxel and imatinib mesylate is still investigational and has been approved for use in
research only.

At least 51 and as many as 65 participants will take part in this study. All participants
will be enrolled and treated at M. D. Anderson.

Inclusion Criteria:

1. Histologically confirmed newly diagnosed (stage IIIC or IV) or recurrent (any stage)
uterine papillary serous carcinoma. Patients with recurrent disease may not have been
treated with taxanes in the past.

2. Patients may not receive concurrent radiotherapy while participating in this protocol.

3. Patients may have measurable or non-measurable disease.

4. Patients may have mixed endometrioid or clear cell components in addition to the
serous histology.

5. Patients' tumor tissue must express one or more of the following biomarkers: c-Kit,
PDGFR-B, or Abl. Positivity will be defined as 2+/3+ intensity in at least 10% of the
tumor.

6. Patients must have pretreatment granulocyte count (i.e. segmented neutrophils and
bands) of >/= 1,500/Fl, a hemoglobin level of >/= 9.0 gm/dl, and a platelet count of
>/= 100,000/Fl.

7. Patients must have an adequate renal function as documented by serum creatinine of

8. Patients must have adequate hepatic function as documented by a serum bilirubin
Alanine aminotransferase (SGPT) and aspartate aminotransferase (SGOT) must be institutional upper limit of normal unless the liver is involved with tumor, in which
case levels must be
9. Zubrod performance status of 0, 1, or 2.

10. Patients should not have received prior chemotherapy or radiation (except palliative
radiation) within the last 30 days.

11. Patients must have signed informed consent indicating that they are aware of the
investigational nature of this study.

Exclusion Criteria:

1. Patients who have previously received imatinib mesylate or taxanes.

2. Patients with any active or uncontrolled systemic infection, including known HIV
infection.

3. Patients with psychiatric disorders that would interfere with consent or follow-up.

4. Patients with New York Heart Association (NYHA) Class III/IV congestive heart failure,
unstable angina or a history of myocardial infarction within the previous 6 months.

5. Patients with a history of prior malignancy except for adequately treated basal cell
or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the
patient has been disease-free for at least three years.

6. Oxygen-dependent lung disease.

7. Patients in whom corticosteroids are contraindicated.

8. Uncontrolled severe hypertension or uncontrolled diabetes mellitus.

9. Presence of clinically apparent central nervous system metastases or carcinomatous
meningitis.

10. Patients with any form of chronic liver disease.

11. Patients with a history of seizures are ineligible. Patients receiving phenytoin,
phenobarbital, or other anti-epileptic prophylaxis are ineligible.

12. Patients with any other severe concurrent disease, which in the judgment of the
investigator, would make the patient inappropriate for entry into this study,
including significant hepatic, renal, or gastrointestinal diseases.

13. Patients with a deep venous or arterial thrombosis (including pulmonary embolism)
within 6 weeks of study entry.

14. Patients who are receiving therapeutic doses of warfarin or any blood thinning agent.

15. Patients with a history of non-compliance with medical regimens or who are considered
potentially unreliable.

16. Pregnant or lactating women. Women of reproductive potential may not participate
unless they have agreed to use an effective contraceptive method.