Paclitaxel and Intraperitoneal Carboplatin Followed by Radiation Therapy in Treating Patients With Stage IIIC-IV Uterine Cancer

PRIMARY OBJECTIVES:

I. To evaluate the toxicity (as defined by National Cancer Institute [NCI] Common Toxicity
Criteria version [v.] 4.0) of weekly intravenous (IV) paclitaxel with intraperitoneal (IP)
carboplatin chemotherapy given every third week, followed by radiation therapy (RT) in
patients with advanced stage uterine serous cancer (USC).

II. To determine the feasibility of this regimen in women with advanced stage USC.

SECONDARY OBJECTIVES:

I. To assess the frequency and the reasons for early discontinuation of the study
treatments.

II. To describe patient-reported quality of life parameters at specified time points during
the study using validated questionnaires: European Organization for Research and the
Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and QLQ-ovarian cancer
module (OV)28.

TERTIARY OBJECTIVES:

I. To define patterns of recurrence (e.g. local versus distant) and progression-free
survival in patients with advanced and recurrent USC treated with dose dense IV paclitaxel
and IP carboplatin therapy.

II. To correlate surrogate endpoint biomarkers that is performed in standard histology
processing (estrogen receptor and progesterone receptor status as well as human epidermal
growth factor 2 [Her2/neu] status) with progression-free survival and prognosis.

III. To assess the potential late effects of combined intraperitoneal chemotherapy and
radiotherapy on the gastrointestinal, genitoureteral, bone marrow and other body systems
beginning at 6 months post treatment completion during routine office visits.

OUTLINE:

CHEMOTHERAPY: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and
15 and carboplatin intraperitoneally (IP) on day 1. Treatment repeats every 21 days for up
to 6 courses (weeks 1-18) in the absence of disease progression or unacceptable toxicity.

RADIATION: At provider discretion, patients may undergo 3-dimensional (3D) conformal or
intensity-modulated radiation therapy (IMRT) 5 days a week for 5 weeks (weeks 19-23).

After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then yearly thereafter for up to 10 years.

Inclusion Criteria:

- Histological/cytologically documented primary International Federation of Gynecology
and Obstetrics (FIGO) stage 3C1, 3C2, stage 4A, and 4B uterine serous carcinoma; in
addition, certain stage 3A and B disease are also allowed

- Residual disease after primary surgery:

- Eligible:

- Stage 3A and B (pelvic, but confined to adnexa or vagina), residual
disease present

- Stage 3CI (pelvic node positive)

- Stage 3CII (para-aortic node positive)

- Stage 4A (bladder or pelvic bowel)

- Stage 4B (distant metastases [mets] including abdominal mets),
completely resected

- Not eligible

- Stage 3A and B (pelvic, but confined to adnexa or vagina), completely
resected

- Stage 4B (distant mets including abdominal mets), residual disease
present

- All patients must have a procedure for determining diagnosis of high-risk uterine
cancer (HRUC); minimum surgical intervention required is tissue biopsy (may be from
endometrium), if significant clinical evidence exists to support a stage 3 or 4
diagnosis; as per the discretion of the surgeon, complete surgical staging should
include: total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal
washings, omental biopsy and lymph node samplings; this is typically the standard
unless the disease is bulky or the clinician feels the patient would be best served
by chemotherapy and radiation therapy after histologic diagnosis is confirmed

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

- Written voluntary informed consent

Exclusion Criteria:

- Distant metastasis to the lung, bone or brain; typically, most stage 4 uterine
papillary serous cancer (UPSC) is confined to the abdomen on presentation

- Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate
transaminase (SGPT) > 2.5 times the institutional upper limit of normal (ULN)

- Total serum bilirubin > 1.5 mg/dl

- Serum creatinine > 2.0 mg/dl

- Platelets < 100,000/mm^3

- Absolute neutrophil count (ANC) < 1500/mm^3

- Hemoglobin < 8.0 g/dl (the patient may be transfused prior to study entry)

- History of abdominal/pelvic radiation therapy

- Severe or uncontrolled, concurrent medical disease (e.g. uncontrolled diabetes,
unstable angina, myocardial infarction within 6 months, congestive heart failure,
etc.)

- Patients with dementia or altered mental status that would prohibit the giving and
understanding of informed consent at the time of study entry