Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Cancer; 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; Recurrence
Intervention: Bevacizumab; Carboplatin; Ixabepilone; Laboratory Biomarker Analysis; Paclitaxel; Temsirolimus
Intervention description: Given IV; Given IV; Given IV; Correlative studies; Given IV; Given IV
Intervention MeSH terms: Sirolimus; Paclitaxel; Epothilones; Epothilone B; Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel; Temsirolimus; Antineoplastic Agents, Immunological; MTOR Inhibitors; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 349.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies paclitaxel, carboplatin, and bevacizumab or
      paclitaxel, carboplatin, and temsirolimus or ixabepilone, carboplatin, and bevacizumab to see
      how well they work in treating patients with stage III, stage IV, or recurrent endometrial
      cancer. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and ixabepilone, 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, may interfere with the
      ability of tumor cells to grow and spread. Temsirolimus may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth. It is not yet known which treatment
      regimen is most effective in treating patients with endometrial cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have measurable stage III, measurable stage IVA, stage IVB (with or
             without measurable disease) or recurrent (with or without measurable disease)
             endometrial carcinoma

               -  Histologic confirmation of the original primary tumor is required; patients with
                  the following histologic epithelial cell types are eligible: endometrioid
                  adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell
                  adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise
                  specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and
                  transitional cell carcinoma

          -  Measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST)
             (version 1.1); measurable disease is defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded); each
             lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance
             imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by
             chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

          -  Patients must have Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

          -  Patients must not be eligible for a higher priority GOG protocol, if one exists; in
             general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol
             for the same patient population

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl equivalent to
             Common Terminology Criteria (CTCAE v3.0) grade 1

          -  Platelets greater than or equal to 100,000/mcl

          -  Creatinine less than or equal to 1.5 times institutional upper limit normal (ULN),
             CTCAE v3.0 grade 1

          -  Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)

          -  Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate
             transaminase (SGPT) less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

          -  Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

          -  Urine protein creatinine (UPC) ratio must be < 1.0 gram (gm); if UPC ratio >= 1,
             collection of 24-hour urine measurement of urine protein is recommended (24-hour urine
             protein level must be < 1000 mg for patient enrollment)

               -  UPC ratio of spot urine is an estimation of the 24 urine protein excretion

                    -  A UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm

          -  Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN
             (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of
             therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 x ULN

          -  Fasting cholesterol less than 300 mg/dL (CTCAE v3.0 grade 1)

          -  Fasting triglycerides =< 2.5 x ULN (CTCAE v3.0 grade 1)

          -  Patients must NOT have received prior chemotherapy or targeted therapy, including
             chemotherapy used for radiation sensitization for treatment of endometrial carcinoma

          -  Patients must NOT have received prior therapy with bevacizumab or other VEGF pathway
             targeted therapy; patients must NOT have received prior therapy with temsirolimus,
             everolimus, ridaforolimus, sirolimus, or any other PI3K/ v-akt murine thymoma viral
             oncogene homolog 1 (AKT)/mammalian target of rapamycins (mTor) pathway targeted
             therapy

          -  Patients may have receive prior radiation therapy for treatment of endometrial
             carcinoma; prior radiation therapy may have included pelvic radiation therapy,
             extended field pelvic/para-aortic radiation therapy, and/or intravaginal
             brachytherapy; all radiation therapy must be completed at least 4 weeks prior to the
             first date of study therapy; the prior radiation field, radiation dose, number of
             fractions and prior radiation start and stop dates must be provided on the Fast Fact
             Sheet (FFS) at registration

          -  Patients may have received prior hormonal therapy for treatment of endometrial
             carcinoma; all hormonal therapy must be discontinued at least one week prior to the
             first date of study therapy

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

        Exclusion Criteria:

          -  Patients with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer, and other specific malignancies as noted below, are excluded
             if there is any evidence of other malignancy being present within the last three
             years; patients are also excluded if their previous cancer treatment contraindicates
             this protocol therapy

          -  Patients who have received prior radiotherapy to any portion of the abdominal cavity
             or pelvis OTHER THAN for the treatment of endometrial cancer within the last three
             years are excluded; prior radiation for localized cancer of the breast, head and neck,
             or skin is permitted, provided that it was completed more than three years prior to
             registration, and the patient remains free of recurrent or metastatic disease

          -  Patients who have received prior chemotherapy for any abdominal or pelvic tumor within
             the last three years are excluded; patients may have received prior adjuvant
             chemotherapy for localized breast cancer, provided that it was completed more than
             three years prior to registration, and that the patient remains free of recurrent or
             metastatic disease

          -  Patients with serious, non-healing wound, ulcer, or bone fracture; this includes
             history of abdominal/pelvic fistula, gastrointestinal perforation or intra-abdominal
             abscess within 3 months prior to the first date of study therapy; patients with
             underlying lesions that caused the fistula or perforation in the past that have not
             been corrected

          -  Patients with active bleeding or pathologic conditions that carry high risk of
             bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
             vessels

          -  Patients with history or evidence upon physical examination of central nervous system
             (CNS) disease, including primary brain tumor, seizures not controlled with standard
             medical therapy or any brain metastases

          -  Patients with clinically significant cardiovascular disease; this includes:

               -  Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm
                  Hg

               -  Myocardial infarction or unstable angina within 6 months of the first date of
                  study therapy

               -  New York Heart Association (NYHA) class II or greater congestive heart failure

               -  History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
                  ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic
                  medications (except for atrial fibrillation that is well controlled with
                  anti-arrhythmic medication)

               -  CTCAE grade 2 or greater peripheral vascular disease.

               -  History of cerebrovascular accident (CVA, stroke), transient ischemic attack
                  (TIA) or subarachnoid hemorrhage within six months of the first date of study
                  therapy.

               -  Aortic aneurysm and/or history of aortic dissection

          -  Patients with known hypersensitivity to Chinese hamster ovary cell products or other
             recombinant human or humanized antibodies

          -  Patients undergoing invasive procedures as defined below:

               -  Major surgical procedure, open biopsy or significant traumatic injury within 28
                  days prior to the first date of bevacizumab or temsirolimus therapy

               -  Major surgical procedure anticipated during the course of the study.

               -  Minor surgical procedures, fine needle aspirates, or core biopsies within 7 days
                  prior to the first date of study therapy

          -  Patients with known prior history of interstitial pneumonitis

          -  Patients with CTCAE v. 3, grade 2 or greater hypoxemia

          -  Patients with CTCAE v. 3, grade 2 or greater dyspnea

          -  Patients must not have uncontrolled diabetes, and must not have baseline hemoglobin
             A1C (HgbA1C) > 8

          -  Patients with peripheral neuropathy > CTCAE v.3, grade 1

          -  Patients who are pregnant or nursing