Inclusion Criteria:

- Histologically confirmed high-risk neuroblastoma and/or demonstration of tumor cells
in the bone marrow with increased urinary catecholamines meeting 1 of the following
criteria:

- Recurrent and/or progressive disease at any time

- Biopsy not required

- Refractory disease (i.e., less than a partial response to frontline therapy,
including a minimum of 4 courses of chemotherapy)

- Biopsy not required

- Persistent disease by MIBG scan, CT and MRI scan, or bone marrow
aspirates/biopsies after ≥ partial response to frontline therapy

- Histologic confirmation of viable neuroblastoma from at ≥ 1 residual site
required

- Tumor seen on routine bone marrow morphology allowed

- Bone marrow immunocytology alone not allowed

- Patients in expansion cohorts 1 and 2 who have had a prior relapse are eligible with
no measurable or evaluable sites of tumor (i.e., in second complete response)

- Patient must have ≥ 1 of the following disease sites (excluding patients on the
expansion cohort):

- Measurable tumor by MRI, CT scan, or X-ray

- MIBG scan with positive uptake at a minimum of 1 site

- Bone marrow with tumor cells seen on routine morphology of 1 bone marrow sample
of a bilateral aspirate and/or biopsy

- Life expectancy ≥ 6 weeks

- Lansky performance status (PS) 50-100% (patients ≤ 16 years of age) OR Karnofsky PS
50-100% (patients > 16 years of age)

- Hemoglobin ≥ 8 g/dL (transfusion allowed)

- ANC ≥ 750/μL

- ANC ≥ 500/μL for patients with marrow metastases

- Platelet count ≥ 50,000/μL (transfusion independent)

- No platelet transfusions within 1 week

- Serum creatinine based on age as follows:

- 0.8 mg/dL (≤ 5 years of age)

- 1.0 mg/dL (> 5 and ≤ 10 years of age)

- 1.2 mg/dL (> 10 and ≤ 15 years of age)

- 1.5 mg/dL (> 15 years of age)

- Hematuria ≤ 1+ and/or proteinuria ≤ 1+

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and AST < 3 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- Serum triglycerides ≤ 300 mg/dL

- Serum calcium < grade 2

- Negative pregnancy test

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Normal ejection fraction (≥ 55%) by echocardiogram or radionuclide MUGA OR normal
fraction shortening (≥ 27%) by echocardiogram

- QTc interval ≤ 450 msec

- No patients who, in the opinion of the investigator, may not be able to comply with
the safety of study requirements

- No disease of any major organ system that would compromise the patient's ability to
withstand therapy

- No active or uncontrolled infection

- Patients on prolonged antifungal therapy allowed provided culture and biopsy are
negative in suspected radiographic lesions

- No allergic reactions to paraben preparations (i.e., Accutane, Sotret)

- Alternate preparations to paraben allowed

- Fully recovered from the acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy

- At least 3 weeks since prior myelosuppressive chemotherapy, including cytotoxic
agents given on a low-dose metronomic regimen

- At least 7 days since prior biologic anti-neoplastic agent (including retinoids)
therapy

- At least 7 days or 3 half-lives, whichever is longer, since prior monoclonal
antibodies

- More than 2 weeks since prior radiotherapy (small-port)

- No prior radiotherapy in patients with 1 site of measurable or evaluable disease
unless that site has demonstrated clear progression after completion of
radiotherapy

- At least 12 weeks since prior large-field radiotherapy (i.e., total-body,
craniospinal, whole abdominal, total lung, or > 50% of marrow space irradiation)

- At least 6 weeks since prior substantial bone marrow radiotherapy

- At least 6 weeks since prior:

- Autologous stem cell infusion following myeloablative therapy

- Allogeneic stem cell transplantation without evidence of active
graft-versus-host disease

- At least 6 weeks since prior ^131I-MIBG therapy

- At least 7 days since prior cytokines or hematopoietic growth factors

- More than 30 days since prior and no concurrent valproic acid

- More than 30 days since prior and no other concurrent investigational medications

- No prior vorinostat combined with isotretinoin

- Prior vorinostat or isotretinoin single-agent or combined with alternative
agents allowed

- No other concurrent anti-cancer agents including chemotherapy, radiotherapy,
biologics, or immunomodulating agents

- No concurrent azole anti-fungal therapy

- No concurrent pentamidine therapy for PCP prophylaxis

- No concurrent enzyme-inducing anti-convulsant therapy