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Childhood Burkitt LymphomaPhase 1NCT00994500

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

A Phase 1 study testing vorinostat, bortezomib and pharmacological study in people with Childhood Burkitt Lymphoma and Childhood Central Nervous System Choriocarcinoma, run by National Cancer Institute (NCI) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
vorinostat, bortezomib and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
6 sitesUnited States
Study dates
Aug 2009to Jul 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

  • 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
Show all 52Show fewer
  • 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)
  • Patients with known bone marrow metastatic disease allowed provided they meet the blood count criteria and are not know to be refractory to RBC or platelet transfusion
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:
  • 0.6 mg/dL (1 to < 2 years of age)
  • 0.8 mg/dL (2 to < 6 years of age)
  • 1.0 mg/dL (6 to < 10 years of age)
  • 1.2 mg/dL (10 to < 13 years of age)
  • 1.5 (male) or 1.4 (female) (13 to < 16 years of age)
  • 1.7 (male) or 1.4 (female) ( ≥ 16 years of age)
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit ofnormal
  • ALT ≤ 110 U/L
  • Serum albumin ≥ 2 g/dL
  • QTc interval ≤ 450 milliseconds
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Must be able to swallow capsules or liquids
  • Able to comply withthe safety-monitoring requirements of the study, in the opinion of the investigator
  • No peripheral neuropathy ≥ grade 2 within the past 14 days
  • No known hypersensitivity to vorinostat or bortezomib
  • No uncontrolled infection
  • No concurrent enzyme-inducing anticonvulsants
  • Must be recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
  • At least 7 days since prior therapy with any of the following:
  • Hematopoietic growth factors
  • Biologic (anti-neoplastic) agent
  • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
  • Corticosteroids unless on a stable or decreasing dose
  • At least 7 days or 3 half-lives, whichever is longer, since prior monoclonal antibodies
  • At least 2 weeks since prior local palliative radiotherapy (small port)
  • At least 6 months since prior total-body irradiation therapy, craniospinal radiotherapy, or ≥ 50% of pelvis irradiated
  • At least 6 weeks since prior substantial bone marrow radiotherapy
  • At least 3 months since prior stem cell transplantation or rescue and no evidence of active graft-vs-host disease
  • At least 2 weeks since prior and no concurrent valproic acid
  • At least 6 weeks since priorimmunotherapy (e.g., tumor vaccines)
  • No prior vorinostat
  • No other concurrent investigational drugs or other anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy

Who cannot join

None listed.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Childrens Memorial Hospital

    Chicago, Illinois, 60614

  • Baylor College of Medicine

    Houston, Texas, 77030

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum-tolerated dose and/or recommended phase II dose of vorinostat in combination with bortezomib in pediatric patients with refractory or recurrent solid tumors, including central nervous system tumors and lymphoma.

II. To define and describe the toxicities of this regimen in these patients. III. To characterize the pharmacokinetics of this regimen in these patients.

SECONDARY OBJECTIVES:

  1. To preliminarily define the antitumor activity of this regimen within the confines of a phase I study.

II. To assess the biologic activity of bortezomib by measuring NF-κB activity in peripheral blood mononuclear cells (PBMC).

III. To assess the biologic activity of bortezomib by measuring endoplasmic reticulum stress response using the GRP78 molecular chaperone marker in PBMC.

OUTLINE: This is a multicenter, dose-escalation study of vorinostat.

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. Blood samples are collected at baseline and during course 1 of study for further analysis.

After completion of study therapy, patients are followed up within 30 days.

Being tested
vorinostat, bortezomib, pharmacological study, laboratory biomarker analysis
Medical subject headings
Burkitt Lymphoma, Choroid Plexus Neoplasms, Lymphoma, Large B-Cell, Diffuse, Meningioma, Lymphoma, Extranodal NK-T-Cell, Oligodendroglioma, Lymphoma, Large-Cell, Anaplastic, Astrocytoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vorinostatDrug

    Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

    Given orally

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00994500
Study groupRoleWhat they receive
Treatment (vorinostat, bortezomib)ExperimentalPatients 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.
Receives: Drug: vorinostat; Drug: bortezomib; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 21 days

Secondary outcomes (1)

  1. Disease response assessed according to RECIST criteria

    Will be reported descriptively.

    Measured: Up to 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2009 (estimated)
  2. Study startAug 2009
  3. Primary completionJul 2011

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00994500
Sponsor's protocol ID
NCI-2011-01980
Other IDs
ADVL0916, CDR0000656719, COG-ADVL0916, U01CA097452
Status last verified
Jul 2013
First submitted
10 Oct 2009
Last updated
2 Jul 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing vorinostat, bortezomib and pharmacological study in people with Childhood Burkitt Lymphoma and Childhood Central Nervous System Choriocarcinoma, run by National Cancer Institute (NCI) at 6 sites 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 52 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 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites 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?

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 (time frame: 21 days). 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 NCT00994500.

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 2013.

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