Concurrent Intensity-Modulated Proton Beam Therapy and High-Dose Chemotherapy for the Treatment of Loco-regionally Advanced Endometrioid Endometrial Cancer, the "UPPROACH" Approach Study

Inclusion Criteria

• Surgery must have included a hysterectomy. Bilateral salpingo-oophorectomy, pelvic lymph node sampling, para-aortic lymph node sampling, and omentectomy are optional
• Patients will be staged according to International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system. Eligibility is defined based on clinical-pathologic features
• Patients with endometrioid endometrial cancer with the following: * Stage IA grade 3 with extensive lymphovascular space invasion (LVSI) * Stage IB grade 3 * Stage II * Stage III (A, B, and C) * Stage IVA who are recommended adjuvant whole pelvic radiation therapy (RT) (+/- lower para-aortic up to renal hilum) and systemic chemotherapy
• Patients with clear cell, serous papillary carcinoma, or carcinosarcoma with stages IA-III who are recommended adjuvant whole pelvic RT (+/- lower para-aortic up to renal hilum) and systemic chemotherapy
• Patients with a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
• White blood count (WBC) >= 3000/mcl
• Absolute neutrophil count (ANC) >= 1000/mcl
• Platelet count >= 100,000/mcl
• Serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and alkaline phosphatase =< 2.5 x upper limit of normal (ULN)
• Bilirubin =< 1.5 x ULN
• Creatinine =< institutional ULN (if serum creatinine > ULN, estimated glomerular filtration rate [GFR] >= 45 ml/min)
• Patients who have signed an approved informed consent and authorization permitting release of personal health information
• Patients must be 18 years of age or older

Exclusion Criteria

• Patients with leiomyosarcoma
• Patients with clinically significant pelvic or para-aortic nodal disease, on post-surgery computed tomography (CT) scan, that was not dissected and would require higher boost dose
• Patients with recurrent endometrial cancer with gross nodal or vaginal disease requiring high dose radiotherapy, or history of prior chemotherapy
• Patients with a history of prior pelvic/abdominal RT or with history of prior cancer treatment that contraindicates this protocol therapy including history of prior chemotherapy for any other malignancy
• 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 a history of myocardial infarction, unstable angina, or uncontrolled arrhythmia within 3 months from enrollment
• Patients recommended to receive concurrent immunotherapy during radiation; though immunotherapy after completion of chemotherapy is allowed, if clinically indicated. Similarly, hormonal therapy or trastuzumab can be added to chemotherapy and radiation (proton or photon) either concurrently or sequentially, if clinically indicated