Temsirolimus in Treating Patients With Recurrent or Persistent Cancer of the Uterus

OBJECTIVES:

- Assess the efficacy of temsirolimus in patients with recurrent or persistent malignant
mixed mesodermal and Mullerian tumors (carcinosarcoma) of the uterus.

- Assess the safety and tolerability of this drug in these patients.

- Evaluate the time to tumor progression in patients treated with this drug.

- Evaluate the progression-free survival (PFS) of patients treated with this drug.

- Evaluate the 6-month PFS rate in patients treated with this drug.

- Evaluate the duration of response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat
every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up periodically for up to 3 years.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed malignant mixed mesodermal and Mullerian
tumors (MMMT) (carcinosarcoma) of the uterus

- Recurrent or persistent disease after primary adjuvant therapy

- Measurable disease

- Patients with lesions measuring ≥ 1 cm to < 2 cm must undergo spiral CT imaging
for both pre- and post-treatment tumor assessments

- Patients who have had prior palliative radiotherapy to metastatic lesion(s) must
have ≥ 1 measurable lesion(s) that has not been previously irradiated

- Tissue samples or blocks from primary tumor or metastases available for tumor studies

- No untreated CNS metastases

- Adequately treated brain metastases allowed provided the following criteria are
met:

- No evidence of progression or hemorrhage after treatment as ascertained by
clinical examination and brain imaging (MRI or CT scan) within the past 12
weeks

- No ongoing requirement for steroids

- Stable dose of anticonvulsants allowed

- No surgical resection of CNS metastases or brain biopsy within the past 3
months

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 75,000/mm^3

- Hemoglobin ≥ 9.0 g/dL

- Direct bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN if liver metastasis is present)

- AST ≤ 2.5 times ULN (≤ 5 times ULN if liver metastasis is present)

- Creatinine ≤ 1.5 times ULN

- Fasting serum cholesterol ≤ 350 mg/dL (9.0 mmol/L)

- Triglycerides ≤ 1.5 times ULN (lipid lowering agents allowed)

- INR ≤ 1.5 (unless on full-dose warfarin)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study therapy

- LVEF normal by MUGA or ECHO within the past 4 weeks (for patients who have had prior
anthracycline)

- Willing to donate blood for correlative studies

- No currently active second malignancy other than nonmelanoma skin cancer

- No other uncontrolled serious medical or psychiatric condition (e.g., cardiac
arrhythmias or diabetes)

- No active infection requiring antibiotics

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No more than 1 prior systemic treatment after primary adjuvant therapy for persistent
or metastatic disease, including any of the following:

- Targeted therapies

- Biologic response modifiers

- Chemotherapy

- Hormonal therapy

- Investigational therapy

- At least 1 week since prior hormonal therapy

- At least 3 weeks since all other prior therapies

- At least 4 weeks since prior adjuvant or palliative radiotherapy

- No prior radiotherapy to any portion of the abdominal cavity or pelvis other than for
the treatment of endometrial cancer

- No prior radiotherapy to > 50% of marrow-bearing areas

- No prior temsirolimus or another mTOR inhibitor

- No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or
phenobarbital) or any other CYP3A4 inducer (e.g., rifampin or St. John wort)

- No concurrent radiotherapy

- Concurrent full-dose anticoagulants allowed provided INR is in range (2-3) AND
patient is on a stable dose of warfarin or low molecular weight heparin

- Concurrent zoledronic acid for bone metastases and/or hypercalcemia allowed provided
it was started before initiation of study treatment