A Phase I Study of Vorinostat and Bortezomib in Children With Refractory of Recurrent Solid Tumors, Including CNS Tumors and Lymphomas
2 other identifiers
interventional
5
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1 lymphoma
Started May 2010
Shorter than P25 for phase_1 lymphoma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 10, 2010
CompletedFirst Submitted
Initial submission to the registry
May 27, 2010
CompletedFirst Posted
Study publicly available on registry
May 28, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 13, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
April 13, 2011
CompletedJuly 2, 2017
April 13, 2011
11 months
May 27, 2010
June 30, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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 Outcomes (1)
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...
Interventions
Eligibility Criteria
You may qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (3)
Emanuele S, Lauricella M, Carlisi D, Vassallo B, D'Anneo A, Di Fazio P, Vento R, Tesoriere G. SAHA induces apoptosis in hepatoma cells and synergistically interacts with the proteasome inhibitor Bortezomib. Apoptosis. 2007 Jul;12(7):1327-38. doi: 10.1007/s10495-007-0063-y.
PMID: 17351739BACKGROUNDPei XY, Dai Y, Grant S. Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors. Clin Cancer Res. 2004 Jun 1;10(11):3839-52. doi: 10.1158/1078-0432.CCR-03-0561.
PMID: 15173093BACKGROUNDMitsiades CS, Mitsiades NS, McMullan CJ, Poulaki V, Shringarpure R, Hideshima T, Akiyama M, Chauhan D, Munshi N, Gu X, Bailey C, Joseph M, Libermann TA, Richon VM, Marks PA, Anderson KC. Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):540-5. doi: 10.1073/pnas.2536759100. Epub 2003 Dec 26.
PMID: 14695887BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
Study Record Dates
First Submitted
May 27, 2010
First Posted
May 28, 2010
Study Start
May 10, 2010
Primary Completion
April 13, 2011
Study Completion
April 13, 2011
Last Updated
July 2, 2017
Record last verified: 2011-04-13