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