A Phase I Study of Vorinostat and Bortezomib in Children With Refractory of Recurrent Solid Tumors, Including CNS Tumors and Lymphomas

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01132911
First received: May 27, 2010
Last updated: April 14, 2011
Last verified: April 2011
  Purpose

Background:

- Vorinostat and bortezomib are anti-tumor drugs that have been approved by the Food and Drug Administration to treat different kinds of myeloma and lymphoma in adults. The combination of these two drugs has been tried in a small number of adults, but it has not been formally approved and is experimental, particularly in children. Researchers are interested in determining safe and effective treatment doses of vorinostat and bortezomib in children, and learning more about how these drugs affect tumor growth and human development.

Objectives:

  • To determine safe and effective doses of vorinostat and bortezomib to treat solid tumors in children.
  • To study the effects of vorinostat and bortezomib on blood cells, blood flow, and human development.

Eligibility:

- Children, adolescents, and young adults between 1 and 21 years of age who have been diagnosed with solid tumors that have not responded to treatment.

Design:

  • Eligible participants will be screened with a physical examination, blood and tumor samples, and imaging studies.
  • Participants will have 21-day treatment cycles of vorinostat and bortezomib. Vorinostat will be given as either tablets or liquid doses on days 1 through 5 and 8 through 12 of each cycle. Bortezomib will be given as an intravenous injection on days 1, 4, 8, and 11 of each cycle. Participants will keep a drug administration diary to record information about side effects or other problems with the treatment.
  • Participants may continue to receive vorinostat and bortezomib for up to 2 years unless serious side effects develop or the tumor does not respond to treatment.
  • Additional blood samples will be taken at regular intervals for the first 3 days after the first bortezomib dose and for the first 2 days after the first vorinostat dose of the first treatment cycle.

Condition Intervention Phase
Lymphoma
Sarcoma
WilmsTumor
Neuroblastoma
Drug: Vorinostat (SAHA)
Drug: Velcade (PS-341, Bortezomib)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Vorinostat and Bortezomib in Children With Refractory of Recurrent Solid Tumors, Including CNS Tumors and Lymphomas

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To determine the maximum tolerated dose and Phase 2 dose of combination vorinostat and bortezomib to children with refractory or recurrent solid tumors.
  • Define toxicities and pharmacokinetics.

Secondary Outcome Measures:
  • To define antitumor activity, assess biological activity of bortezomib by measuring NF-kb activity in PBMC and to assess the biologic activity of bortezomib by measuring endoplasmic reticulum stress response using GRP78 molecular chaperone marke...

Estimated Enrollment: 5
Study Start Date: May 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Vorinostat (SAHA)
    N/A
    Drug: Velcade (PS-341, Bortezomib)
    N/A
Detailed Description:

Background:

-The combination of vorinostat and bortezomib has been shown to be synergistic in vitro in a variety of malignancies, including hepatoma, multiple myeloma, leukemia, lymphoma, and gastrointestinal cancer. Currently several phase 2 adult studies are underway evaluating combination therapy.

Objectives:

  • To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of the combination of oral vorinostat administered on days 1-5 and 8-12 and bortezomib administered intravenously on days 1, 4, 8, 11, every 21 days to children with refractory or recurrent solid tumors.
  • To define and describe the toxicities of vorinostat in combination with bortezomib administered on this schedule.
  • To characterize the pharmacokinetics of vorinostat and bortezomib in combination in children with refractory or recurrent solid tumors.
  • Secondary objectives include preliminary definition of the antitumor activity of these agents when administered together; and assessment of the biologic activity of bortezomib by measuring NF-kappaB activity in peripheral blood mononuclear cells (PBMC) and by measuring endoplasmic reticulum stress response using the GRP78 molecular chaperone marker in PBMC.

Eligibility:

  • Patients greater than12 months and less than or equal to 21 years of age with a diagnosis and histologic verification (except patients with instrinsic brain stem tumors, optic pathway gliomas or pineal tumors) of measureable or evaluable relapsed or refractory solid tumors including CNS tumors and lymphomas are eligible. Current disease state must be one for which there is no known curative therapy, or therapy proven to prolong survival.
  • Performance score: Karnofsky greater than or equal to 60% for patients greater than 16 years of age; Lansky greater than or equal to 60 for patients less than or equal to 16 years of age.
  • Must have fully recovered from acute toxic effects from all prior therapy which have been completed within the specified prior time frame. Have adequate organ function as determined by laboratory evaluation.

Design:

  • This is a phase I study of vorinostat administered orally once daily on days 1-5 and day 8-12 in combination with bortezomib administered intravenously on days 1, 4, 8, and 11 of a 21 day cycle. Disease evaluation will be performed after cycle 1 and then every 2 cycles thereafter.
  • Therapy may continue for up to 2 years in the absence of progressive disease or unacceptable toxicity.
  • Optional participation in correlative biology studies or pharmacokinetic studies will be offered.
  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • Eligibility Criteria:

Inclusion Criteria:

  • Patients older than12 months and less than or equal to 21 years of age with a diagnosis and histologic verification (except patients with instrinsic brain stem tumors, optic pathway gliomas or pineal tumors) of measureable or evaluable relapsed or refractory solid tumors including CNS tumors and lymphomas are eligible.
  • Current disease state must be one for which there is no known curative therapy, or therapy proven to prolong survival.
  • Performance score: Karnofsky greater than or equal to 60% for patients greater than 16 years of age; Lansky greater than or equal to 60 for patients less than or equal to 16 years of age.
  • Must have fully recovered from acute toxic effects from all prior therapy which have been completed within the specified prior time frame.
  • Have adequate organ function as determined by laboratory evaluation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01132911

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01132911     History of Changes
Other Study ID Numbers: 100119, 10-C-0119
Study First Received: May 27, 2010
Last Updated: April 14, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Solid Tumors
Maximum Tolerated Dose
Lymphoma
Dose Escalation
Pharmacokinetics
Pediatric Cancer
Solid Tumor
Sarcoma
Wilms Tumor
Neuroblastoma

Additional relevant MeSH terms:
Sarcoma
Neuroblastoma
Lymphoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Vorinostat
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014