Most pediatric patients with solid tumors respond to initial high-dose, intensive therapy and
      complete treatment in remission. High-risk patients however, frequently have recurrent
      disease which is then treated with ad hoc regimens or early phase therapies with little
      benefit to the patient. Metronomic therapy (MC), defined as lower dose continuous drug
      exposure, has been successfully tested in pediatric leukemias with excellent results in terms
      of improved outcome, toxicity profiles, and cost. MC has been applied to solid tumors with
      little success, but has been implemented usually in the relapsed setting at a time of high
      tumor burden and disease resistance. This protocol's overall objective is to improve on
      historical outcome for high risk pediatric patients who are in remission by initiating MC
      treatment after completion of front-line therapy.

      This protocol 1) will treat patients when they have minimal disease burden, 2) will treat
      patients with agents either not previously incorporated into front-line therapy or given in a
      different manner and, 3) is designed to be given in the outpatient setting. The 4 agents will
      take advantage of targeting frequently disrupted signaling pathways, epigenetic
      abnormalities, and classical cell killing mechanisms. An analysis of cost will be undertaken
      to help define part of the financial impact to families and on the health care system to
      deliver this therapy. The hypothesis of this protocol is: Introduction of metronomic
      treatment after completion of standard therapy for patients with high-risk, solid tumors in
      remission will improve time to tumor progression compared with historical controls. The
      primary and secondary goals (specific aims) of this protocol are: To determine the time to
      tumor progression for patients at high-risk of relapse with solid tumors; To define and
      describe the toxicity profile of the chemotherapy regimen; To determine the site(s) of
      relapse for patients receiving treatment;To determine part of the cost of delivering
      treatment; and finally to understand how this added therapy impacts quality of life.

      Chemotherapy will be started within 6 weeks of completion of front-line treatment,
      documentation of remission status and fulfillment of all eligibility criteria. Documentation
      of remission will be by appropriate evaluations including history, physical examination,
      laboratory testing and radiographic imaging and follow criteria for initial staging, when
      appropriate.

      There will be two study blocks. Each block will be of 21 days duration consisting of 14
      treatment days followed by 7 rest days. The following block will start on day 22 of the
      cycle. There will be 10 cycles of therapy (approximately 60 weeks) and each cycle is defined
      by 42 days. Each block will be separated by a 1 week rest period (no chemotherapy) and
      patients will be evaluated for disease status every two cycles of therapy. Therapy will
      continue for 10 cycles or until patients relapse or are intolerant of therapy.

      Block A consists of bevacizumab weekly X 2 weeks at 10 mg/kg, IV, on days 1 and 8, and oral
      cyclophosphamide X 14 days at 25 mg/m2, on days 1-14. The maximum dose of cyclophosphamide
      will be 50 mg. Block B will consist of temsirolimus weekly X 2 weeks, 25 mg/m2, IV, on days
      22 and 29, and valproic acid, 5 mg/kg, by mouth, on days 22-35. Valproic acid trough levels
      will be maintained at 75-100 ucg/mL by adjusting doses as appropriate. The rest periods are
      on days 15-21 and 36-42.

      Blocks of chemotherapy interrupted because of toxicity will not be repeated or time extended
      to complete. The next block will be started when toxicity has improved to grade II or less
      and if two blocks of treatment are interrupted for toxicity, dose reductions instituted as
      defined in this protocol.

      Additionally, subjects enrolled on MC and a control group will complete three quality of life
      (PedsQL) instruments at three study time points: PedsQL Cancer Module, PedsQL Fatigue Module,
      and the Present Functioning scale. These indicators will assess how added therapy has
      impacted quality of life.

      There are no investigational procedures, and no placebo involved in this protocol.

      The potential benefits of this protocol are prolongation of remission status for the patient
      with minimal toxicity, few anticipated hospitalizations and minimal additional cost of care.
      Some patients may be cured as a result of this treatment. Should this study improve outcome
      for this group of patients, the benefits to society would be great. Outcome for high risk
      patients has stagnated for at least the last 10 years and additional high-dose chemotherapy
      is unlikely to improve outcome because of poor tolerability (side effects). Studying some of
      the cost associated with this treatment is important because of the lack of information on
      out-patient care cost in general and to understand the economic impact on families and
      society.