Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

NCT00994500 | Completed Phase 1

• 5 other identifiers: NCI-2011-01980ADVL0916CDR0000656719COG-ADVL0916U01CA097452
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 6

Brief Summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with bortezomib in treating young patients with refractory or recurrent solid tumors, including CNS tumors and lymphoma. Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Conditions

Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell 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 Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; 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 Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose defined as the maximum dose at which fewer than one-third of patients experience DLT according to NCI CTCAE version 3.0

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

  21 days

Secondary Outcomes (1)

• Disease response assessed according to RECIST criteria

  Up to 30 days

Study Arms (1)

Treatment (vorinostat, bortezomib)

EXPERIMENTAL

Patients receive oral vorinostat once daily on days 1-5 and 8-12 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: vorinostat; Drug: bortezomib; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

vorinostat DRUG

Given orally

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

Treatment (vorinostat, bortezomib)

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE

Treatment (vorinostat, bortezomib)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (vorinostat, bortezomib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (vorinostat, bortezomib)

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 solid tumors, including CNS tumors or lymphoma
• Histological confirmation not required for the following diagnoses
• Intrinsic brain stem tumors
• Optic pathway gliomas
• Pineal tumors and elevations of cerebral spinal fluid or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin, allowed
• Relapsed or refractory disease
• Must have measurable or evaluable tumor
• No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Karnofsky performance status (PS) 60-100% for patients \> 16 years of age OR Lansky PS60-100% for patients ≤ 16 years of age
• Neurologic deficits inpatients with CNS tumors must have been relatively stable for a minimum of 1week
• Patients who are unable to walk because ofparalysis, but who are up in a wheelchair, will be considered ambulatory for thepurpose of assessing the performance score
• ANC ≥ 1,000/μL
• Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions within the past 7 days)
• Patients with known bone marrow metastatic disease allowed provided they meet the blood count criteria and are not known to be refractory to platelet transfusion
• Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

Childrens Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, 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

MeSH Terms

Conditions

Burkitt Lymphoma; Choroid Plexus Neoplasms; Lymphoma, Large B-Cell, Diffuse; Meningioma; Lymphoma, Extranodal NK-T-Cell; Oligodendroglioma; Lymphoma, Large-Cell, Anaplastic; Astrocytoma; Familial ependymoma; Dendritic Cell Sarcoma, Interdigitating; Medulloblastoma; Optic Nerve Glioma; Recurrence

Interventions

Vorinostat; Bortezomib

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cerebral Ventricle Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Nerve Tissue; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Lymphoma, T-Cell; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Histiocytic Disorders, Malignant; Histiocytosis; Neuroectodermal Tumors, Primitive; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jodi Muscal

  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: October 10, 2009
• First Posted: October 14, 2009
• Study Start: August 1, 2009
• Primary Completion: July 1, 2011
• Last Updated: July 2, 2013

Record last verified: 2013-07

Locations

US (6)