A Feasibility Trial Using Molecular-Guided Therapy for the Treatment of Patients With Relapsed and Refractory Childhood Cancer

Inclusion Criteria:

- Subjects must have histologically proven neuroblastoma, brain tumor, or rare tumor
and confirmation of refractory or recurrent disease with histologic confirmation at
diagnosis or at the time of recurrence/progression

- Subjects must be age >12 months at enrollment.

- Subjects must be age ≤ 21 years at initial diagnosis.

- Subjects must have measurable disease as demonstrated by residual abnormal tissue at
a primary or metastatic site measuring more than 1 cm in any dimension by
standardized imaging (CT or MRI); tumor must be accessible for biopsy. Patients with
bone marrow only disease expected to be >75% tumor are eligible to enroll.

- Current disease state must be one for which there is currently no known curative
therapy

- Lansky or Karnofsky Score must be more than 50

- Subjects without bone marrow metastases must have an ANC > 750/μl

- Adequate liver function must be demonstrated, defined as:

1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND

2. SGPT (ALT) < 10 x upper limit of normal (ULN) for age

- A negative serum pregnancy test is required for female participants of child bearing
potential (≥13 years of age or after onset of menses)

- Both male and female post-pubertal study subjects need to agree to use one of the
more effective birth control methods during treatment and for six months after
treatment is stopped. These methods include total abstinence (no sex), oral
contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants
(Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of
these cannot be used, contraceptive foam with a condom is recommended.

- Informed Consent: All subjects and/or legal guardians must sign informed written
consent. Assent, when appropriate, will be obtained according to institutional
guidelines. Voluntary consent for optional biology studies will be included.

Exclusion Criteria:

- Subjects who have received any cytotoxic chemotherapy within the last 7 days prior to
enrollment and 14 days prior to study treatment start date.

- Subjects who have received any radiotherapy to the primary sample site within the
last 14 days (radiation may be included in treatment decision after biopsy).

- Subjects receiving anti-tumor therapy for their disease or any investigational drug
concurrently

- Subjects with serious infection or a life-threatening illness (unrelated to tumor)
that is > Grade 2 (NCI CTCAE V4.0), or active, serious infections requiring
parenteral antibiotic therapy.

- Subjects with any other medical condition, including malabsorption syndromes, mental
illness or substance abuse, deemed by the Investigator to be likely to interfere with
the interpretation of the results or which would interfere with a subject's ability
to sign or the legal guardian's ability to sign the informed consent, and subject's
ability to cooperate and participate in the study