Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer

Inclusion Criteria:

• Histologically confirmed endometrial cancer, including 1 of the following cellular types:

  • Endometrioid endometrial adenocarcinoma
  • Clear cell carcinoma
  • Papillary serous adenocarcinoma
  • Adenosquamous cell carcinoma
  • Other adenocarcinoma variant
• No carcinosarcoma

• Meets 1 of the following criteria:

  • Grade 3 carcinoma with > 50% myometrial invasion (stage IC or IIA) (all papillary serous or clear cell carcinoma will be considered grade 3)
  • Grade 2 or 3 carcinoma with any cervical stromal invasion (stage IIB)

  • Known extra-uterine disease confined to the pelvis (stage III or IVA)

    • Patients with stage III or IVA disease must have undergone CT scan or PET/CT scan of the abdomen and pelvis within the past 56 days
• Has undergone hysterectomy (i.e., total abdominal, vaginal, robotic-assisted, radical, or laparoscopic-assisted vaginal hysterectomy) and bilateral salpingo-oophorectomy within the past 56 days
• No positive common iliac or positive para-aortic nodal disease (defined as lymph nodes ≥ 2 cm in any dimension on CT scan or biopsy) or positive peritoneal cytology
• No evidence of metastatic extrauterine disease, gross or residual disease (not including pelvic nodal disease), or distant metastases
• Zubrod performance status 0-1
• ANC ≥ 1,500/mm^3 (without growth factor support)
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2 times ULN
• Serum creatinine ≤ 1.5 mg/dL
• Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg on 24-hour urine collection
• INR < 1.5 (for patients treated with warfarin within the past 14 days)
• Not nursing
• No neuropathy ≥ CTCAE grade 1
• No ototoxicity > CTCAE grade 2

• No serious, active comorbidity, including any of the following:

  • Unstable angina and/or NYHA class II-IV congestive heart failure requiring hospitalization within the past 12 months
  • Transmural myocardial infarction within the past 12 months
  • Acute bacterial or fungal infection requiring IV antibiotics
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • AIDS based upon current CDC definition (HIV testing is not required)
  • Active gastrointestinal (GI) ulcers, GI bleeding, inflammatory bowel disease, or GI obstruction
  • Inadequately controlled hypertension, defined as systolic BP > 150 mm Hg and/or diastolic BP > 90 mm Hg on antihypertensive medications
  • Significant vascular disease, including aortic aneurysm, aortic dissection, or arteriovenous malformation within the past 12 months
  • Serious cardiac arrhythmia on medication (well-controlled atrial fibrillation on medication allowed)
  • Serious non-healing wound, ulcer, or bone fracture
• No history of hypertensive crisis or hypertensive encephalopathy
• No stroke/cerebrovascular event within the past 12 months
• No arterial thromboembolic events, including transient ischemic attack or clinically symptomatic peripheral artery disease within the past 12 months
• No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 6 months
• No other invasive malignancies within the past 3 years other than nonmelanomatous skin cancer
• No significant trauma within the past 28 days
• No mental status changes or bladder problems that would preclude the ability to comply with bladder-filling instructions
• No mental or psychiatric illness that would preclude giving informed consent
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No prior allergic reaction to bevacizumab, cisplatin, carboplatin, or paclitaxel
• No concurrent erythropoietin, St. John's wort, therapeutic anticoagulants, aminoglycoside antibiotics, or amifostine
• No prior organ transplantation
• No prior external-beam radiotherapy to the pelvis resulting in overlapping of radiotherapy fields

• No prior systemic chemotherapy for uterine cancer

  • Prior chemotherapy for a different cancer is allowed
• No prior therapy with anti-VEGF compounds
• More than 28 days since prior major surgical procedure requiring open biopsy incision
• No concurrent surgery (except for vascular access device placement or procedures that do not require significant incision)

• No concurrent warfarin at doses > 1 mg/day

  • Concurrent prophylactic low molecular weight heparin allowed