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Childhood Atypical Teratoid/Rhabdoid TumorPhase 1NCT01076530

Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

A Phase 1 study testing vorinostat, temozolomide and diagnostic laboratory biomarker analysis in people with Childhood Atypical Teratoid/Rhabdoid Tumor and Childhood Central Nervous System Choriocarcinoma, run by National Cancer Institute (NCI) at 9 sites in 2 countries.

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 temozolomide in treating young patients with relapsed or refractory primary brain tumors or spinal cord tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
vorinostat, temozolomide and diagnostic laboratory biomarker analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
9 sitesin 2 countries
Study dates
Feb 2010to Oct 2012
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 CNS malignancy at original diagnosis or relapse
  • Histologic confirmation not required for patients with intrinsic brain stem tumors, optic pathway gliomas, or pineal tumors provided CSF or serum tumor markers, including alpha-fetoprotein orbeta-HCG, are elevated
  • Recurrent or refractory spinal cord tumors allowed
  • Measurable or evaluable disease
  • No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)
Show all 46Show fewer
  • Neurological deficits must have been relatively stable for ≥ 1 week before study entry
  • Patients unable to walk due to paralysis, but who are up in a wheelchair, are considered ambulatory for the purpose of assessing performance status
  • ANC ≥ 1,000/μL
  • Platelet count ≥ 100,000/μL (transfusion independent, defined as no platelet transfusion within the past 7 days)
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
  • Creatinine clearance or radioisotope GFR ≥ 70mL/min OR maximum serum creatinine based on age and/or gender as follows:
  • 0.6 mg/dL (1 year of age)
  • 0.8 mg/dL (2 to 5 years of age)
  • 1.0 mg/dL (6 to 9 years of age)
  • 1.2 mg/dL (10 to 12 years of age)
  • 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years of age)
  • 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years of age)
  • Bilirubin ≤ 1.5 times upper limit of normal
  • ALT ≤ 110 U/L
  • Serum albumin ≥ 2 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to swallow capsules or liquid
  • Seizure disorder allowed provided it is well controlled with nonenzyme-inducing anticonvulsants
  • No pre-existing QTc ≥ 450 msec
  • No uncontrolled infection
  • No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of study
  • Fully recovered from prior chemotherapy, immunotherapy, or radiotherapy
  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
  • At least 7 days since prior hematopoietic growth factors
  • At least 7 days since prior biologic agent (antineoplastic agent)
  • At least 7 days or 3 half-lives, whichever is longer, since prior monoclonal antibodies
  • More than 2 weeks since prior local palliative radiotherapy (small port)
  • At least 6 months since prior total-body radiotherapy (TBI), craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • At least 3 months since prior stem cell transplantation or rescue (without TBI)
  • No evidence of active graft-vs-host disease
  • At least 2 weeks since prior valproic acid
  • No prior vorinostat
  • Prior temozolomide allowed provided there was no progressive disease during or within 1 month after completion of treatment
  • Concurrent corticosteroids allowed provided patient has been on a stable or decreasing dose for ≥ 7 days before study entry
  • No other concurrent investigational drugs
  • No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
  • No concurrent enzyme-inducing anticonvulsants

Who cannot join

None listed.

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States7 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Childrens Memorial Hospital

    Chicago, Illinois, 60614

  • Baylor College of Medicine

    Houston, Texas, 77030

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Minnesota Medical Center-Fairview

    Minneapolis, Minnesota, 55455

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Seattle Children's Hospital

    Seattle, Washington, 98105

Other trials in United States

Canada2 sites

  • Hospital Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: A Phase I Study of SAHA and Temozolomide in Children With Relapsed or Refractory Primary Brain or Spinal Cord Tumors

This phase I trial is studying the side effects and best dose of vorinostat when given together with temozolomide in treating young patients with relapsed or refractory primary brain tumors or spinal cord tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may help temozolomide work better by making tumor cells more sensitive to the drug.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum tolerated dose and/or recommended phase II dose of vorinostat in combination with temozolomide in pediatric patients with relapsed or refractory primary CNS tumors.

II. To define and describe the toxicities 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 characterize the pharmacokinetic parameters of vorinostat in these patients.

III. To determine whether acetylated histones in peripheral blood mononuclear cells can be identified as a surrogate marker of the biologic effect of vorinostat at various treatment doses.

IV. To assess the feasibility of collecting and analyzing serum DNA for methylation of the MGMT promoter and describe the relationship between promoter methylation and clinical responses within the confines of this phase I study.

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

Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses repeat every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood sample collection periodically for pharmacokinetic and correlative laboratory studies by western blotting and MGMT promoter methylation assays.

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

Being tested
vorinostat, temozolomide, diagnostic laboratory biomarker analysis, pharmacological study
Medical subject headings
Rhabdoid Tumor, Choroid Plexus Neoplasms, Astrocytoma, Oligodendroglioma, Paraganglioma, Extra-Adrenal, Familial ependymoma, Medulloblastoma, Spinal Cord Neoplasms

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

  • temozolomideDrug

    Also called SCH 52365, Temodal, Temodar, TMZ

  • diagnostic laboratory biomarker analysisOther

  • pharmacological studyOther

    Also called pharmacological studies

Study groups in NCT01076530
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses repeat every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: vorinostat; Drug: temozolomide; Other: diagnostic laboratory biomarker analysis; Other: pharmacological study

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 using NCI CTCAE version 4.0

    In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.

    Measured: 28 days

  2. Pharmacokinetic parameters of vorinostat in combination with temozolomide

    The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

    Measured: Pre-dose, 15 and 30 minutes, 1, 2, 4, 6, 8, and 24 hours

Secondary outcomes (1)

  1. 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 posted26 Feb 2010 (estimated)
  2. Study startFeb 2010
  3. Primary completionOct 2012

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
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01076530
Sponsor's protocol ID
NCI-2011-02011
Other IDs
ADVL0819, CDR0000664388, COG-ADVL0819, U01CA097452
Status last verified
May 2013
First submitted
25 Feb 2010
Last updated
3 May 2013
Results posted
No

Publications

  • Hummel TR, Wagner L, Ahern C, Fouladi M, Reid JM, McGovern RM, Ames MM, Gilbertson RJ, Horton T, Ingle AM, Weigel B, Blaney SM. A pediatric phase 1 trial of vorinostat and temozolomide in relapsed or refractory primary brain or spinal cord tumors: a Children's Oncology Group phase 1 consortium study. Pediatr Blood Cancer. 2013 Sep;60(9):1452-7. doi: 10.1002/pbc.24541. Epub 2013 Mar 28.

    PubMed 23554030

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing vorinostat, temozolomide and diagnostic laboratory biomarker analysis in people with Childhood Atypical Teratoid/Rhabdoid Tumor and Childhood Central Nervous System Choriocarcinoma, run by National Cancer Institute (NCI) at 9 sites in 2 countries.

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 46 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 3 May 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada. 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 using NCI CTCAE version 4.0 (time frame: 28 days). 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 NCT01076530, which also lists 1 linked publication.

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 3 May 2013.

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