Overview

This trial is active, not recruiting.

Conditions untreated childhood medulloblastoma, untreated childhood pineoblastoma, untreated childhood supratentorial primitive neuroectodermal tumor
Treatments 3-dimensional conformal radiation therapy, carboplatin, cisplatin, cyclophosphamide, etoposide phosphate, isotretinoin, laboratory biomarker analysis, peripheral blood stem cell transplantation, thiotepa, vincristine sulfate, vorinostat
Target HDAC
Sponsor National Cancer Institute (NCI)
Start date February 2009
End date January 2017
Trial size 62 participants
Trial identifier NCT00867178, NCI-2012-03167, PBTC-026, U01CA081457, UM1CA081457

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
See Detailed Description
3-dimensional conformal radiation therapy 3-dimensional radiation therapy
Undergo conformal radiation therapy
carboplatin Blastocarb
Given IV
cisplatin Abiplatin
Given IV
cyclophosphamide (-)-Cyclophosphamide
Given IV
etoposide phosphate Etopophos
Given IV
isotretinoin 13-cis retinoic acid
Given PO
laboratory biomarker analysis
Correlative studies
peripheral blood stem cell transplantation PBPC transplantation
Undergo PBSC
thiotepa 1,1',1''-Phosphinothioylidynetrisaziridine
Given IV
vincristine sulfate Kyocristine
Given IV
vorinostat L-001079038
Given PO

Primary Outcomes

Measure
Dose-limiting toxicity of proposed vorinostat as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
time frame: Up to 21 days
Feasibility in terms of completing 3 courses of induction therapy
time frame: Within 98 days
Prognostic value of histopathological classification of pediatric medulloblastoma by single-nucleotide polymorphism (SNP) analysis and gene expression analysis
time frame: Up to 5 years

Secondary Outcomes

Measure
Overall survival (OS)
time frame: Up to 5 years
Predictive values of biological markers in CSF, plasma and urine in the context of a feasibility study
time frame: Up to 5 years
Progression-free survival (PFS)
time frame: Up to 5 years
Response rate of this approach in patients with measurable residual disease (primary site and/or metastatic sites)
time frame: Up to 5 years

Eligibility Criteria

Male or female participants from 2 months up to 47 months old.

Inclusion Criteria: - Patients must have a histologically confirmed, newly-diagnosed medulloblastoma (except for patients with the histology of localized (M0) desmoplastic medulloblastoma or atypical teratoid/rhabdoid tumor [ATRT]) or supratentorial primitive neuroectodermal tumor (PNET) including pineoblastomas - Patients must have not received any prior therapy other than surgery and/or steroids - Patient must have adequate pre-trial formalin-fixed, paraffin-embedded (FFPE) tumor material available for use in the biology studies and central pathology review; if snap frozen tissue is not available, the study chair must be contacted to discuss eligibility - Patient must be a suitable candidate, by institutional standards for stem cell apheresis - Lansky performance score (LPS for =< 16 years of age) >= 30 assessed within two weeks prior to registration - Absolute neutrophil count (ANC) >= 1000/ul (unsupported) - Platelets >= 100,000/ul (unsupported) - Hemoglobin >= 8 g/dL (may be supported) - Bilirubin < 1.5 times upper limit of normal for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 1.5 times institutional upper limit of normal for age - Serum creatinine =< 1.5 times upper limit of institutional normal for age or glomerular filtration rate (GFR) >= 70 ml/min/1.73m^2 or estimated GFR (Schwartz bedside) that is > 99 ml/min/1.73m^2 - Parents/legal guardians must have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines Exclusion Criteria: - Patients with diagnosis of atypical teratoid/rhabdoid tumor (ATRT by histology, immunohistochemistry and/or molecular analysis) and desmoplastic M0 medulloblastoma will be excluded from the study - Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would interfere with the study procedures or results - Patients receiving any other anticancer or investigational drug therapy are excluded - Patients having taken valproic acid within 2 weeks prior to initiation of treatment are excluded - Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy - Patients with a parabens allergy

Additional Information

Official title A Feasibility Study of Vorinostat (SAHA) Combined With Isotretinoin and Chemotherapy in Infants With Embryonal Tumors of the Central Nervous System
Principal investigator Sarah Leary
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 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. 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 courses 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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).