Ensayos clínicos

Study closed to enrollment

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