Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: DFMO; Etoposide
Intervention description: Escalating doses of DFMO in a 3 +3 cohort design.
DFMO at current cohort Dose Level orally each day for 21 day cycles
Dose level 1: 500 mg/m2 PO BID Dose level 2: 750 mg/m2 PO BID Dose level 3:1000 mg/m2 PO BID Dose level 4:1500 mg/m2 PO BID; Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.
Intervention MeSH terms: Eflornithine; Etoposide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Healthy volunteers: No
Keywords: Refractory Neuroblastoma; Relapsed neuroblastoma

Summary:

      The purpose of this research study is to evaluate a new investigational drug to treat
      neuroblastoma. This study drug is called DFMO. The objectives of this study will be to
      monitor for safety and to find a maximum tolerated dose in this population. A secondary
      objective will be to look at efficacy of DFMO.

      The safety of the proposed dosing regimen in this trial will be tested by an on-going
      risk/benefit assessment during the study. A patient benefiting from treatment, not
      progressing on therapy, and in the absence of any safety issues associated with DFMO and/or
      etoposide may continue on treatment with the expectation that there will be an overall
      clinical benefit.

      The procedures involved in this study include Medical history, Physical exam, Vital signs
      (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the
      tumor(s), MIBG scans, and Bone marrow aspirations. All of these tests and procedures are
      considered standard of care for this population. Drug administration is also part of this
      protocol, including an investigational new drug called DFMO, and later combined with an
      already approved drug, etoposide.

      The proposed dosing regimen is an oral dose of DFMO two times a day for each day while on
      study. There will be 5 cycles. Each cycle will be 21 days in length. The first cycle will be
      DFMO alone. In the second cycle etoposide will be added in and will be given orally once a
      day for the first 14 days of each cycle (cycles 2-5).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age: 0-21 years at the time of diagnosis.

          -  Diagnosis: Histologic verification at either the time of original diagnosis or relapse
             of neuroblastoma.

          -  Disease Status: Refractory or relapsed neuroblastoma

          -  Measurable disease, including at least one of the following:

        Measurable tumor >10mm by CT or MRI A positive MIBG and abnormal urinary catecholamine
        levels Positive bone marrow biopsy/aspirate.

          -  Current disease state must be one for which there is currently no known curative
             therapy.

          -  A negative urine pregnancy test is required for female subjects of child bearing
             potential (onset of menses or ≥13 years of age).

          -  Patients without bone marrow metastases must have an ANC > 500/μl and platelet count
             >50,000/μl

          -  Organ Function Requirements Subjects must have adequate liver function as defined by
             AST or ALT <10x normal Serum bilirubin must be ≤ 2.0 mg/dl Serum creatinine must be ≥
             1.5 mg/dl

          -  Informed Consent: All subjects and/or legal guardians must sign informed written
             consent. Assent, when appropriate, will be obtained according to institutional
             guidelines

        Exclusion Criteria:

          -  Life expectancy <2 months or Lansky score <30%

          -  Investigational Drugs: Subjects who are currently receiving another investigational
             drug are excluded from participation.

          -  Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are
             not eligible. Subjects must have fully recovered from the effects of prior
             chemotherapy (hematological and bone marrow suppression effects)

          -  Infection: Subjects who have an uncontrolled infection are not eligible until the
             infection is judged to be well controlled in the opinion of the investigator.

          -  Subjects who, in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study, or in whom compliance is likely to be
             suboptimal, should be excluded.