Intraperitoneal Paclitaxel, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Stage III-IV Endometrial Cancer

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of intraperitoneal (IP) paclitaxel when given
concurrently with fixed dose intravenous (IV) doxorubicin (doxorubicin hydrochloride) and IV
cisplatin.

II. To determine the maximum tolerated dose of IP paclitaxel when given concurrently with
fixed dose IV doxorubicin hydrochloride and IP cisplatin.

III. To determine the feasibility of an IV/IP based doxorubicin hydrochloride, paclitaxel,
and cisplatin chemotherapy regimen in patients with advanced endometrial cancer.

OUTLINE: This is a dose-escalation study of paclitaxel.

Patients receive doxorubicin hydrochloride IV over 30 minutes followed by cisplatin IV over 1
hour on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim subcutaneously (SC) on
days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for up to 2 courses
in the absence of disease progression or unacceptable toxicity.

Patients then receive doxorubicin hydrochloride IV and cisplatin IV or IP on day 1, and
paclitaxel IP on days 1 or 8. Treatment repeats every 21 days for up to 4 courses in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Inclusion Criteria:

- Patients with stage IIIA, or stage IIIC with positive cytologic washings/ascites,
adnexal spread, or serosal involvement, or stage IV (by virtue of intraperitoneal
disease spread) histologically confirmed endometrial cancer (endometrioid, serous,
clear cell, squamous/adenosquamous, undifferentiated, or mixed histologies)

- Patients must be optimally cytoreduced with less than or equal to 2 cm residual
disease

- Absolute neutrophil count (ANC) greater than or equal to 1,500/mm^3, equivalent to
Common Toxicity Criteria (Common Terminology Criteria for Adverse Events [CTCAE]
version 3.0 [v3.0]) grade 1

- Platelets greater than or equal to 100,000/mm^3 (CTCAE v3.0 grade 0-1)

- Hemoglobin greater than or equal to 10 g/dl (CTCAE v3.0 grade 1)

- Creatinine less than or equal to 2 mg/% or 24 hour creatinine clearance > 50 ml/min

- Bilirubin less than or equal to 1.5 x upper limit of normal (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)

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

- Patients must have normal ejection fraction

- Patients must be enrolled within 8 weeks of surgery

- Patients who have met the pre-entry requirements

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

- Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

Exclusion Criteria:

- Metastatic disease involving lung or liver parenchyma, bone or inguinal or scalene
lymph nodes

- Patients with GOG performance grade of 3 or 4

- Patients with concomitant medical illness such as serious uncontrolled infection,
uncontrolled angina, or serious peripheral neuropathy, which in the opinion of the
treating physician, makes the protocol prescribed treatments hazardous to the patient

- Patients with 3rd degree or complete heart block are not eligible unless a pacemaker
is in place; patients who are on medications which alter cardiac conduction
(digitalis, beta blockers, calcium channel blockers) or who have other cardiac
conduction abnormalities may be placed on study at the discretion of the investigator

- Patients with a history of other invasive malignancies, with the exception of
non-melanoma skin cancer, are excluded if there is any evidence of other malignancy
being present within the last five years; patients are also excluded if their previous
cancer treatment contraindicates this protocol therapy

- Patients who have received prior radiation or chemotherapy for the cancer being
treated in this study