Vinorelbine Tartrate and Cyclophosphamide in Combination With Bevacizumab or Temsirolimus in Treating Patients With Recurrent or Refractory Rhabdomyosarcoma

Inclusion Criteria:

   - Diagnosis

      - Patients with first relapse or progression of rhabdomyosarcoma are eligible

      - Patients with primary refractory disease are eligible

         - Primary refractory disease is defined as first progression after receiving
         at least one course of cyclophosphamide or ifosfamide containing
         chemotherapy without prior demonstration of a radiographic response to
         chemotherapy (progression on irinotecan-containing chemotherapy without
         cyclophosphamide or ifosfamide containing chemotherapy will not be
         considered a first progression)

      - Note: Patients without measurable or evaluable disease are eligible

   - Patients must have had a previous histological verification of rhabdomyosarcoma at
   original diagnosis

   - Patients must have a Karnofsky or Lansky performance status score of >= 50%,
   corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2;
   use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of
   age

   - Patients must have a life expectancy of >= 8 weeks

   - Patients must have fully recovered from the acute toxic effects of all prior
   chemotherapy, immunotherapy, or radiotherapy prior to entering this study

   - Myelosuppressive chemotherapy: Must not have received within 3 weeks prior to entry
   onto this study (4 weeks if prior nitrosourea)

   - Biologic (anti-neoplastic agent):

      - Patients may have received prior therapy with oral tyrosine kinase inhibitors or
      other similar agents; at least 7 days must have elapsed since the completion of
      therapy with a biologic agent and all toxicities must have resolved to < grade 2
      prior to enrollment

      - 3 half-lives (or 6 weeks) must have elapsed since previous monoclonal antibody
      therapy prior to enrollment on this study

   - Myeloid growth factor: Must not have received within 1 week prior to entry onto this
   study

   - Radiation therapy (RT): At least 4 weeks must have elapsed between RT and study entry;
   previously radiated lesions cannot be used to assess response unless those sites are
   the sites of disease progression

   - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed; for
   allogeneic SCT, >= 6 months must have elapsed and no evidence of active graft vs. host
   disease

   - Patients must have recovered from any surgical procedure before enrolling on this
   study

      - Minor surgical procedures (e.g., biopsies involving core or fine-needle
      aspiration procedures, infusaport or Broviac line placement, paracentesis, or
      thoracocentesis) need to have fully healed and occurred > 7 days prior to
      enrollment

      - Patients who have had a major surgical procedure (such as laparotomy,
      thoracotomy, open biopsy, or resection of tumor) can only be enrolled on study >
      28 days from such procedure

   - Peripheral absolute neutrophil count (ANC) >= 750/μL

   - Platelet count >= 75,000/μL (transfusion independent, defined as without transfusion
   for >= 1 week prior to enrollment)

   - Hemoglobin >= 8.0 g/dL (may receive packed red blood cells [PRBC] transfusions)

   - Bone marrow disease involvement of tumor is allowed, however, peripheral blood count
   criteria must still be met

   - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
   mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows:

      - =< 0.4 mg/dL (for patients aged 1 month to < 6 months)

      - =< 0.5 mg/dL (for patients aged 6 months to < 1 year)

      - =< 0.6 mg/dL (for patients aged 1 to < 2 years)

      - =< 0.8 mg/dL (for patients aged 2 to < 6 years)

      - =< 1 mg/dL (for patients aged 6 to < 10 years)

      - =< 1.2 mg/dL (for patients aged 10 to < 13 years)

      - =< 1.4 mg/dL (for female patients aged >= 13 years)

      - =< 1.5 mg/dL (for male patients aged 13 to < 16 years)

      - =< 1.7 mg/dL (for male patients aged >= 16 years)

   - Urine protein level:

      - Patients aged =< 17 years: Urine protein to creatinine (UPC) ratio should be
      calculated; UPC ratio must be =< 1 for patient to be eligible

      - Patients aged > 17 years: Urine protein should be screened by urine analysis; if
      protein is 2+ or higher, 24-hour urine protein must be obtained and the level
      must be < 1,000 mg for patient enrollment

   - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

   - Shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by
   radionuclide angiogram

Exclusion Criteria:

   - Patients with botryoid histology, any stage or group, are ineligible

   - Patients with embryonal histology, stage I or clinical group 1 at initial disease
   presentation, who present with local or regional recurrence, are ineligible

   - Patients who previously received craniospinal irradiation are ineligible

   - Patients who previously received vinorelbine, bevacizumab, temsirolimus, or any other
   direct vascular endothelial growth factor (VEGF)/vascular endothelial growth factor
   receptor (VEGFR-) or mammalian target of rapamycin (mTOR-) targeting agents are
   ineligible

   - Patients with known central nervous system (CNS) disease (excluding
   intracranial/intraspinal extension secondary to local progression of a parameningeal
   or paraspinal primary), except for those with treated brain metastasis, are ineligible

      - Treated brain metastases are defined as having no ongoing requirement for
      steroids and no evidence of progression or hemorrhage after treatment for at
      least 3 months, as ascertained by clinical examination and brain imaging
      (magnetic resonance imaging [MRI] or computed tomography [CT]); stable dose of
      anticonvulsants are allowed; treatment for brain metastases may include
      whole-brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear
      accelerator [LINAC], or equivalent), or a combination as deemed appropriate by
      the treating physician

      - Patients with CNS metastases treated within 3 months prior to enrollment by
      neurosurgical resection or brain biopsy are ineligible

   - Patients who receive radiation or chemotherapy (inclusive of palliative intent) for
   first disease progression or relapse of rhabdomyosarcoma prior to enrollment are
   ineligible

   - Female patients who are pregnant are ineligible

   - Lactating females are not eligible unless they have agreed to discontinue
   breastfeeding

   - Female patients of childbearing potential are not eligible unless a negative pregnancy
   test result has been obtained

   - Sexually active patients of reproductive potential are not eligible unless they have
   agreed to use an effective contraceptive method for the duration of their study
   participation

   - Patients with a documented chronic non-healing wound, ulcer, or significant trauma
   injury (those with bone fractures, including pathological fractures, or requiring
   surgical intervention) within 28 days prior to beginning therapy are ineligible

   - Patients with evidence of intratumoral hemorrhage, gastrointestinal bleeding, or on
   anticoagulation for thrombosis or history of thrombosis are ineligible

   - Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension is
   defined as follows:

      - Patients aged =< 17 years: greater than 95th percentile systolic and diastolic
      blood pressure based on age and height that is not controlled by one
      antihypertensive medication

      - Patients aged > 17 years: systolic blood pressure >= 160 mm Hg and/or diastolic
      blood pressure >= 90 mm Hg that is not controlled by one antihypertensive
      medication

   - Patients currently taking anticoagulants or antiplatelet agents with the exception of
   aspirin (=< 81 mg/day) are ineligible

   - Patients with history of central venous catheter (CVC)-associated thrombosis requiring
   systemic anticoagulation are ineligible; Note: Patients with history of sluggish flow
   from CVC or CVC-associated thrombosis treated with tissue plasminogen activator (TPA)
   only are not excluded

   - Patients with clinically significant cardiovascular disease are excluded:

      - History of cerebrovascular accident (CVA) within the prior 6 months

      - Myocardial infarction or unstable angina within the prior 6 months

      - New York Heart Association grade 2 or greater congestive heart failure

      - Serious and inadequately controlled cardiac arrhythmia

      - Significant vascular disease (e.g., aortic aneurysm, history of aortic
      dissection)

      - Clinically significant peripheral vascular disease

   - Patients diagnosed with rhabdomyosarcoma as a second malignant neoplasm are not
   eligible

   - Patients with history of any second malignant neoplasm who have received chemotherapy
   or radiation for the treatment of that malignancy are not eligible