Trial Information

A Feasibility Study of SAHA Combined With Isotretinoin and Chemotherapy in Infants With Embryonal Tumors of the Central Nervous System

PRIMARY OBJECTIVES:

I. To investigate the feasibility of administering SAHA and Isotretinoin for three days
prior and concomitant with cisplatin based chemotherapy over three courses of induction
chemotherapy.

II. To describe the toxicity of administering SAHA and Isotretinoin for three days prior and
concomitant with cisplatin based chemotherapy over three courses of induction chemotherapy.

III. To investigate prognostic values of histopathological classification and biological
markers in the context of a feasibility study.

SECONDARY OBJECTIVES:

I. To estimate the preliminary response rate of this approach in patients with measurable
residual disease (primary site and/or metastatic sites).

II. To estimate disease specific progression-free and overall survival, in the context of a
feasibility study.

III. To explore the predictive values of biological markers in CSF, plasma, urine tumor
material in the context of a feasibility study.

OUTLINE: This is a multicenter study.

Induction therapy: Patients receive oral vorinostat once daily and oral isotretinoin twice
daily on days 1-4; vincristine sulfate IV on days 4, 11, and 18; cisplatin IV over 6 hours
on day 4; cyclophosphamide IV over 1 hour on days 5-6; and etoposide phosphate IV over 1
hour on days 4-6. Treatment repeats every 21 days for 3 courses in the absence of disease
progression or unacceptable toxicity. Patients also undergo peripheral blood stem cell
(PBSC) harvesting after each course.

Consolidation therapy: Within 6 weeks (10 weeks if patient is re-staged) after completion of
induction therapy, patients receive carboplatin IV over 2 hours and thiotepa IV over 2 hours
on days 1-2. Patients also receive autologous PBSC rescue infusion over 6 hours on day 4.
Treatment repeats every 28 days for 3 courses in the absence of disease progression or
unacceptable toxicity. Patients with M0 non-desmoplastic medulloblastoma also undergo
conformal radiotherapy* to the tumor bed.

NOTE: *Patients with supratentorial primary tumors or metastatic disease undergo
radiotherapy at the discretion of treating physician.

Maintenance therapy: Beginning 4 weeks after completion of radiotherapy or immediately after
completion of consolidation therapy, patients receive oral vorinostat once daily on days 1,
3, 5, 6, 8, 10, 12, and oral isotretinoin twice daily on days 1-14. Treatment repeats every
28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Tumor tissue and peripheral blood mononuclear cells are collected at baseline for gene
expression analysis (by SNP array and tissue microarray) and protein and signaling pathway
expression via IHC and FISH.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for 3 years.