A Phase I Study of Vorinostat and Bortezomib in Children With Refractory of Recurrent Solid Tumors, Including CNS Tumors and Lymphomas
| Status: | Archived |
|---|---|
| Conditions: | Cancer, Brain Cancer, Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | May 2010 |
| End Date: | March 2012 |
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.
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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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