Vorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System
Condition: Medulloblastoma; Pineoblastoma; Supratentorial Embryonal Tumor, Not Otherwise Specified
MeSH terms: Medulloblastoma; Pinealoma; Neoplasms, Germ Cell and Embryonal; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This pilot clinical trial studies the side effects and the best way to give vorinostat with
      isotretinoin and combination chemotherapy and to see how well they work in treating younger
      patients with embryonal tumors of the central nervous system. Vorinostat may stop the growth
      of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in
      chemotherapy, such as isotretinoin, vincristine sulfate, cisplatin, cyclophosphamide, and
      etoposide phosphate, work in different ways to stop the growth of tumor cells, either by
      killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving
      vorinostat with isotretinoin and combination chemotherapy may be an effective treatment for
      embryonal tumors of the central nervous system. A peripheral blood stem cell transplant may
      be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow
      more chemotherapy to be given so that more tumor cells are killed.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To investigate the feasibility of administering vorinostat (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 vorinostat (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 cerebrospinal fluid (CSF),
      plasma, urine tumor material in the context of a feasibility study.

      OUTLINE:

      INDUCTION THERAPY: Patients receive vorinostat orally (PO) once daily (QD) and isotretinoin
      PO twice daily (BID) on days 1-4; vincristine sulfate intravenously (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 cycles
      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 cycles in the absence of disease progression or
      unacceptable toxicity. Beginning 3 weeks later, 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 vorinostat PO QD on days 1, 3, 5, 6, 8,
      10, 12, and 13 and isotretinoin PO BID on days 1-14. Treatment repeats every 28 days for up
      to 12 cycles in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years and
      then every 6 months for 3 years.
    

Intervention name(s): 3-Dimensional Conformal Radiation Therapy; Carboplatin; Cisplatin; Cyclophosphamide; Etoposide Phosphate; Isotretinoin; Laboratory Biomarker Analysis; Peripheral Blood Stem Cell Transplantation; Thiotepa; Vincristine Sulfate; Vorinostat
Intervention type(s): Radiation; Drug; Drug; Drug; Drug; Drug; Other; Procedure; Drug; Drug; Drug
Intervention description(s): Undergo conformal radiation therapy; Given IV; Given IV; Given IV; Given IV; Given PO; Correlative studies; Undergo PBSC; Given IV; Given IV; Given PO
Other intervention name(s): 3-dimensional radiation therapy; 3D Conformal; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy; Radiation, 3D Conformal; Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Abiplatin; Blastolem; Briplatin; CDDP; Cis-diammine-dichloroplatinum; Cis-diamminedichloridoplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cismaplat; Cisplatina; Cisplatinum; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Neoplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Etopophos; 13-cis retinoic acid; 13-cis-Retinoate; 13-cis-Retinoic Acid; 13-cis-Vitamin A Acid; 13-cRA; Absorica; Accure; Accutane; Amnesteem; cis-Retinoic Acid; Cistane; Claravis; Isotretinoinum; Isotrex; Isotrexin; Myorisan; Neovitamin A; Neovitamin A Acid; Oratane; Retinoicacid-13-cis; Ro 4-3780; Ro-4-3780; Roaccutan; Roaccutane; Roacutan; Sotret; ZENATANE; PBPC transplantation; PBSCT; Peripheral Blood Progenitor Cell Transplantation; PERIPHERAL BLOOD STEM CELL TRANSPLANT; Peripheral Stem Cell Support; Peripheral Stem Cell Transplant; Peripheral Stem Cell Transplantation; 1,1',1''-Phosphinothioylidynetrisaziridine; Girostan; N,N', N''-Triethylenethiophosphoramide; Oncotiotepa; STEPA; Tepadina; TESPA; Tespamin; Tespamine; Thio-Tepa; Thiofosfamide; Thiofozil; Thiophosphamide; Thiophosphoramide; Thiotef; Tifosyl; TIO TEF; Tio-tef; Triethylene Thiophosphoramide; Triethylenethiophosphoramide; Tris(1-aziridinyl)phosphine sulfide; TSPA; WR 45312; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; L-001079038; MSK-390; SAHA; Suberanilohydroxamic Acid; Suberoylanilide Hydroxamic Acid; Zolinza
Intervention MeSH terms: Vitamin A; Cyclophosphamide; Thiotepa; Cisplatin; Carboplatin; Etoposide; Vincristine; Vorinostat; Tretinoin; Etoposide phosphate; Isotretinoin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment