Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7
MeSH terms: Adenocarcinoma; Endometrial Neoplasms; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Carcinoma, Adenosquamous
Intervention: Bevacizumab; Carboplatin; Cisplatin; Intensity-Modulated Radiation Therapy; Paclitaxel
Intervention description: Given IV; Given IV; Given IV; Undergo IMRT; Given IV
Intervention MeSH terms: Paclitaxel; Bevacizumab; Cisplatin; Carboplatin; Albumin-Bound Paclitaxel; Antineoplastic Agents, Immunological; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects of giving intensity-modulated radiation therapy
      together with cisplatin and bevacizumab followed by carboplatin and cisplatin and to see how
      well they work in treating patients who have undergone surgery for high-risk endometrial
      cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the
      tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in
      chemotherapy, such as cisplatin, carboplatin, and paclitaxel, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Monoclonal antibodies, such as bevacizumab, can block the ability of tumor cells to grow and
      spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the
      tumor. Giving intensity-modulated radiation therapy together with chemotherapy and
      bevacizumab after surgery may kill any tumor cells that remain after surgery.
    

Eligibility criteria:

        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 computed
                       tomography (CT) scan or positron emission tomography (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

          -  Absolute neutrophil count (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)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (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

          -  International normalized ratio (INR) < 1.5 (for patients treated with warfarin within
             the past 14 days)

          -  Not nursing

          -  No neuropathy ? Common Terminology Criteria for Adverse Events (CTCAE) grade 1

          -  No ototoxicity > CTCAE grade 2

          -  No serious, active comorbidity, including any of the following:

               -  Unstable angina and/or New York Heart Association (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

               -  Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease
                  Control (CDC) definition (human immunodeficiency virus [HIV] testing is not
                  required)

               -  Active gastrointestinal (GI) ulcers, GI bleeding, inflammatory bowel disease, or
                  GI obstruction

               -  Inadequately controlled hypertension, defined as systolic blood pressure (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-vascular endothelial growth factor (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