Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

This randomized phase III trial studies carboplatin and paclitaxel to see how well they work with or without cisplatin and radiation therapy in treating patients with stage I-IVA endometrial cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether carboplatin and paclitaxel are more effective with or without cisplatin and radiation therapy in treating patients with endometrial cancer.

PRIMARY OBJECTIVES:

I. To determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (experimental arm) reduces the rate of recurrence or death (i.e., increases recurrence-free survival) when compared to chemotherapy consisting of carboplatin and paclitaxel for 6 cycles (control arm) in patients with stages III-IVA endometrial carcinoma (\< 2 cm residual disease) or patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I or II serous (uterine papillary serous carcinoma \[UPSC\]) or clear cell endometrial carcinoma and positive cytology.

SECONDARY OBJECTIVES:

I. To determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (experimental arm) reduces the rate of death (i.e., increases survival) when compared to chemotherapy consisting of carboplatin and paclitaxel for 6 cycles (control arm) in patients with stages III-IVA endometrial carcinoma (\< 2 cm residual disease) or patients with FIGO 2009 stage I or II serous (UPSC) or clear cell endometrial carcinoma and positive cytology.

II. To compare the regimens with respect to acute and late adverse effects of therapy.

III. To determine the impact of patient-reported quality of life during and following treatment for up to 1 year with the two treatment regimens.

TERTIARY OBJECTIVES:

I. To bank formalin-fixed, paraffin-embedded (FFPE) tumor tissue and whole blood specimens for future research.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cisplatin intravenously (IV) on days 1 and 29. Patients also undergo radiation therapy once daily (QD), 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

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

Eligibility Criteria:
Inclusion Criteria:

* All patients with surgical stage III or IVA endometrial carcinoma per FIGO 2009 staging criteria including clear cell and serous papillary and undifferentiated carcinoma

  * Surgical stage III disease includes those patients with positive adnexa, parametrial involvement, tumor invading the serosa, positive pelvic and/or para-aortic nodes, or vaginal involvement
  * Surgical stage IVA patients with bladder or bowel mucosal involvement, but no spread outside the pelvis
* Patients with FIGO 2009 surgical stage I or II endometrial clear cell or serous carcinoma and with positive peritoneal cytology
* Surgery must have included a hysterectomy and bilateral salpingo-oophorectomy; pelvic lymph node sampling and para-aortic lymph node sampling are optional
* Patients with a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
* White blood cell (WBC) \>= 3,000/mcl
* Absolute neutrophil count (ANC) \>= 1,500/mcl
* Platelet count \>= 100,000/mcl
* Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x upper limit of normal (ULN)
* Alkaline phosphatase =\< 2.5 times ULN
* Bilirubin =\< 1.5 times ULN
* Creatinine =\< institutional ULN
* Patients who have met the pre-entry requirements; testing values/results must meet eligibility criteria
* Patients who have signed an approved informed consent and authorization permitting release of personal health information
* Entry into the study is limited to no more than 8 weeks from the date of surgery

Exclusion Criteria:

* Patients with carcinosarcoma
* Patients with recurrent endometrial cancer
* Patients with residual tumor after surgery (any single site) exceeding 2 cm in maximum dimension
* Patients who have had pelvic or abdominal radiation therapy
* Patients with positive pelvic washings as the only extra-uterine disease are NOT eligible if the histology is other than clear cell or papillary serous carcinoma
* Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of active malignancy within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
* Patients with a history of serious co-morbid illness or uncontrolled illnesses that would preclude protocol therapy
* Patients with an estimated survival of less than three months
* Patients with FIGO 2009 stage IVB endometrial cancer
* Patients with parenchymal liver metastases
* Patients who have received prior chemotherapy for endometrial cancer
* Patients with a history of myocardial infarction, unstable angina, or uncontrolled arrhythmia within 3 months from enrollment