Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

NCT01076530 | Completed Phase 1

• 5 other identifiers: NCI-2011-02011ADVL0819CDR0000664388COG-ADVL0819U01CA097452
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 9

Brief Summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with temozolomide in treating young patients with relapsed or refractory primary brain tumors or spinal cord tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may help temozolomide work better by making tumor cells more sensitive to the drug.

Conditions

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose defined as the maximum dose at which fewer than one-third of patients experience DLT using NCI CTCAE version 4.0

  In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.

  28 days

• Pharmacokinetic parameters of vorinostat in combination with temozolomide

  The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  Pre-dose, 15 and 30 minutes, 1, 2, 4, 6, 8, and 24 hours

Secondary Outcomes (1)

• Response assessed according to RECIST criteria

  Up to 30 days

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses repeat every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Drug: vorinostat; Drug: temozolomide; Other: diagnostic laboratory biomarker analysis; Other: pharmacological study

Interventions

vorinostat DRUG

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Arm I

temozolomide DRUG

Also known as: SCH 52365, Temodal, Temodar, TMZ

Arm I

diagnostic laboratory biomarker analysis OTHER

Arm I

pharmacological study OTHER

Also known as: pharmacological studies

Arm I

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Histologically confirmed CNS malignancy at original diagnosis or relapse
• Histologic confirmation not required for patients with intrinsic brain stem tumors, optic pathway gliomas, or pineal tumors provided CSF or serum tumor markers, including alpha-fetoprotein orbeta-HCG, are elevated
• Recurrent or refractory spinal cord tumors allowed
• Measurable or evaluable disease
• No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Karnofsky performance status (PS) 50-100% (for patients \> 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)
• Neurological deficits must have been relatively stable for ≥ 1 week before study entry
• Patients unable to walk due to paralysis, but who are up in a wheelchair, are considered ambulatory for the purpose of assessing performance status
• ANC ≥ 1,000/μL
• Platelet count ≥ 100,000/μL (transfusion independent, defined as no platelet transfusion within the past 7 days)
• Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
• Creatinine clearance or radioisotope GFR ≥ 70mL/min OR maximum serum creatinine based on age and/or gender as follows:
• mg/dL (1 year of age)
• mg/dL (2 to 5 years of age)
• mg/dL (6 to 9 years of age)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

Childrens Memorial Hospital

Chicago, Illinois, 60614, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hospital Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• Hummel TR, Wagner L, Ahern C, Fouladi M, Reid JM, McGovern RM, Ames MM, Gilbertson RJ, Horton T, Ingle AM, Weigel B, Blaney SM. A pediatric phase 1 trial of vorinostat and temozolomide in relapsed or refractory primary brain or spinal cord tumors: a Children's Oncology Group phase 1 consortium study. Pediatr Blood Cancer. 2013 Sep;60(9):1452-7. doi: 10.1002/pbc.24541. Epub 2013 Mar 28.

  PMID: 23554030 DERIVED

MeSH Terms

Conditions

Rhabdoid Tumor; Choroid Plexus Neoplasms; Astrocytoma; Oligodendroglioma; Paraganglioma, Extra-Adrenal; Familial ependymoma; Medulloblastoma; Spinal Cord Neoplasms; Optic Nerve Glioma

Interventions

Vorinostat; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Cerebral Ventricle Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Paraganglioma; Neuroendocrine Tumors; Neuroectodermal Tumors, Primitive; Spinal Cord Diseases; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Trent Hummel

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2010
• First Posted: February 26, 2010
• Study Start: February 1, 2010
• Primary Completion: October 1, 2012
• Last Updated: May 3, 2013

Record last verified: 2013-05

Locations

CA (2); US (7)