Imatinib Mesylate in Treating Patients With Recurrent or Persistent Uterine Cancer

PRIMARY OBJECTIVES:

I. To determine the activity of Gleevec^trademark (TM) (imatinib mesylate) as measured by
progression-free survival at six months.

II. To determine the frequency and severity of adverse effects of Gleevec^TM in this cohort
of patients as assessed by the Common Terminology Criteria of Adverse Events version 3.0
(CTCAE v3.0).

SECONDARY OBJECTIVES:

I. To determine the distribution of progression-free survival and overall survival.

II. To estimate the objective response rate (partial and complete response as defined under
the Response Evaluation Criteria In Solid Tumors [RECIST] criteria).

III. To determine the effects of prognostic factors such as initial performance status and
histological grade.

TERTIARY OBJECTIVES:

I. To determine the levels of expression of v-kit Hardy-Zuckerman 4 feline sarcoma viral
oncogene homolog (c-KIT), platelet-derived growth factor receptor (PDGFR), v-akt murine
thymoma viral oncogene homolog 2 (AKT2), and phosphorylated (p)-AKT2 in archived,
formalin-fixed, paraffin-embedded primary tumors collected prior to the initiation of
first-line chemotherapy

OUTLINE:

Patients receive imatinib mesylate orally (PO) once daily (QD) or twice daily (BID) on days
1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.

Inclusion Criteria:

- Patients must have histologically confirmed uterine carcinosarcoma that is persistent
or recurrent with documented disease progression after appropriate local therapy;
acceptable histologic type is defined as carcinosarcoma (malignant mixed Mullerian
tumor), homologous or heterologous type

- All patients must have measurable disease; measurable disease is defined as at least
one lesion that can be accurately measured in at least one dimension (longest
dimension to be recorded); each lesion must be >= 20 mm when measured by conventional
techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic
resonance imaging (MRI), or >= 10 mm when measured by spiral CT

- Patients must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST; tumors within a previously irradiated field will be
designated as "non-target" lesions

- Patients must not be eligible for a higher priority Gynecological Oncology Group (GOG)
protocol, if one exists; in general, this would refer to any active GOG phase III
protocol for the same patient population

- Patients who have received one prior regimen must have a GOG performance status of 0,
1, or 2; patients who have received two prior regimens must have a GOG performance
status of 0 or 1

- Recovery from effects of recent surgery, radiotherapy, or chemotherapy

- Patients should be free of active infection requiring antibiotics

- Any hormonal therapy directed at the malignant tumor must be discontinued at
least one week prior to registration; continuation of hormone replacement therapy
is permitted

- Any other prior therapy directed at the malignant tumor, including immunologic
agents, must be discontinued at least three weeks prior to registration

- Patients must have had one prior chemotherapeutic regimen for management of
carcinosarcoma; initial treatment may include high-dose therapy, consolidation, or
extended therapy administered after surgical or non-surgical assessment

- Patients are allowed to receive, but are not required to receive, one additional
cytotoxic regimen for management of recurrent or persistent disease according to the
following definition:

- Cytotoxic regimens include any agent that targets the genetic and/or mitotic
apparatus of dividing cells, resulting in dose-limiting toxicity to the bone
marrow and/or gastrointestinal mucosa

- Note: Patients on this non-cytotoxic study are allowed to receive one additional
cytotoxic chemotherapy regimen for management of recurrent or persistent disease,
as defined above; however, due to the novel nature of biologic compounds,
patients are encouraged to enroll on second-line non-cytotoxic studies prior to
receiving additional cytotoxic therapy

- Patients must have NOT received any non-cytotoxic chemotherapy for management of
recurrent or persistent disease

- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to
CTCAE v3.0 grade 1

- Platelets greater than or equal to 100,000/mcl

- Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE
v3.0 grade 1

- Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)

- Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 x ULN (CTCAE
v3.0 grade 1)

- Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

- Neuropathy (sensory and motor) less than or equal to CTCAE v3.0 grade 1

- Patients must have signed an approved informed consent and authorization permitting
release of personal health information

- Patients who have met the pre-entry requirements

- Patients of childbearing potential must have a negative serum pregnancy test prior to
the study entry and be practicing an effective form of contraception, and cannot be
lactating; since interactions with the metabolism of oral contraceptives cannot be
excluded, a barrier method of contraception must be used

- Patients must have tissue blocks from initial diagnosis available for submission to
the GOG Tissue Bank

Exclusion Criteria:

- Patients who had previous treatment with Gleevec^TM

- Patients with other invasive malignancies, with the exception of non-melanoma skin
cancer, who had (or have) any evidence of other cancer present within the last 5 years
or whose previous cancer treatment contraindicates this protocol therapy

- Patients with signs or symptoms of bowel dysfunction or obstruction

- Patients receiving therapeutic anticoagulation with warfarin

- Patients with deep venous or arterial thrombosis (including pulmonary embolism) within
six weeks of study entry

- Patients receiving therapeutic corticosteroids

- Patients with active or uncontrolled infection

- History of seizures or those patients receiving phenytoin, phenobarbital, or
carbamazepine

- Patients with other severe concurrent disease, which the investigator feels may make
the patients inappropriate for study entry

- Presence of clinically apparent central nervous system metastases, or other
carcinomatous meningitis

- History of myocardial infarction within previous six months or congestive heart
failure requiring therapy