LymphomaPhase 1NCT01132911
A Phase I Study of Vorinostat and Bortezomib in Children With Refractory of Recurrent Solid Tumors, Including CNS Tumors and Lymphomas
A Phase 1 study testing Vorinostat (SAHA) and Velcade (PS-341, Bortezomib) in people with Lymphoma and Sarcoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Lymphoma, Sarcoma, WilmsTumor
- What is being tested?
- Vorinostat (SAHA) and Velcade (PS-341, Bortezomib)
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 10 May 2010to 13 Apr 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Lymphoma, Sarcoma, WilmsTumor, Neuroblastoma
- Being tested
- Vorinostat (SAHA), Velcade (PS-341, Bortezomib)
- Keywords
- Solid Tumors, Maximum Tolerated Dose, Lymphoma, Dose Escalation, Pharmacokinetics, Pediatric Cancer, Solid Tumor, Sarcoma, Wilms Tumor, Neuroblastoma
- Medical subject headings
- Lymphoma, Sarcoma, Neuroblastoma, Neoplasms, Wilms Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vorinostat (SAHA)Drug
Velcade (PS-341, Bortezomib)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
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...
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2010 (estimated)
- Study start10 May 2010
- Primary completion13 Apr 2011
- Study completion13 Apr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01132911
- Sponsor's protocol ID
- 100119
- Other IDs
- 10-C-0119
- Status last verified
- 13 Apr 2011
- First submitted
- 27 May 2010
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
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.
PubMed 17351739Pei 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.
PubMed 15173093Mitsiades 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.
PubMed 14695887
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Vorinostat and Bortezomib in Children With Refractory of Recurrent Solid Tumors, Including CNS Tumors and Lymphomas
- ClinicalTrials.gov ID
- NCT01132911
- Acronym / sponsor ID
- 100119
- Conditions
- Lymphoma, Sarcoma, WilmsTumor, Neuroblastoma
- Keywords
- Solid Tumors, Maximum Tolerated Dose, Lymphoma, Dose Escalation, Pharmacokinetics, Pediatric Cancer, Solid Tumor, Sarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 10 May 2010
- Primary completion
- 13 Apr 2011 (actual)
- Study completion
- 13 Apr 2011 (actual)
- First posted
- 28 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vorinostat (SAHA) | Drug | – |
| Velcade (PS-341, Bortezomib) | Drug | – |
Primary outcome
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.
1 secondary outcome
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...
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 17351739Emanuele 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.
- Background: PubMed 15173093Pei 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.
- Background: PubMed 14695887Mitsiades 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vorinostat (SAHA) and Velcade (PS-341, Bortezomib) in people with Lymphoma and Sarcoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the maximum tolerated dose and Phase 2 dose of combination vorinostat and bortezomib to children with refractory or recurrent solid tumors.. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01132911, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.