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MedulloblastomaPhase 1NCT00867178

Vorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System

A Phase 1 study testing 3-Dimensional Conformal Radiation Therapy, Carboplatin and Cisplatin in people with Medulloblastoma and Pineoblastoma, run by National Cancer Institute (NCI) at 15 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 pilot clinical trial studies the side effects and the best way to give vorinostat with isotretinoin and combination chemotherapy and to see how well they work in treating younger patients with embryonal tumors of the central nervous system. Read more about this study

Who is it for?
Ages 2 to 47 months
What is being tested?
3-Dimensional Conformal Radiation Therapy, Carboplatin and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
15 sitesUnited States
Study dates
25 Feb 2009to 22 Dec 2021
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 2 to 47 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Patients must have a histologically confirmed, newly-diagnosed medulloblastoma (except for patients with the histology of localized (M0) desmoplastic medulloblastoma or atypical teratoid/rhabdoid tumor [ATRT]) or supratentorial primitive neuroectodermal tumor (PNET) including pineoblastomas
  • Patients must have not received any prior therapy other than surgery and/or steroids
  • Patient must have adequate pre-trial formalin-fixed, paraffin-embedded (FFPE) tumor material available for use in the biology studies and central pathology review; if snap frozen tissue is not available, the study chair must be contacted to discuss eligibility
  • Patient must be a suitable candidate, by institutional standards for stem cell apheresis
  • Lansky performance score (LPS for =< 16 years of age) >= 30 assessed within two weeks prior to registration
  • Absolute neutrophil count (ANC) >= 1000/ul (unsupported) (within 14 days of registration and within 7 days of the start of treatment)
Show all 12Show fewer
  • Platelets >= 100,000/ul (unsupported) (within 14 days of registration and within 7 days of the start of treatment)
  • Hemoglobin >= 8 g/dL (may be supported) (within 14 days of registration and within 7 days of the start of treatment)
  • Bilirubin < 1.5 times upper limit of normal for age (within 14 days of registration and within 7 days of the start of treatment)
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 1.5 times institutional upper limit of normal for age (within 14 days of registration and within 7 days of the start of treatment)
  • Serum creatinine =< 1.5 times upper limit of institutional normal for age or glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or estimated GFR (Schwartz bedside) that is > 99 ml/min/1.73 m^2 (within 14 days of registration and within 7 days of the start of treatment)
  • Parents/legal guardians must have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines

Who cannot join

  • Patients with diagnosis of atypical teratoid/rhabdoid tumor (ATRT by histology, immunohistochemistry and/or molecular analysis) and desmoplastic M0 medulloblastoma will be excluded from the study
  • Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would interfere with the study procedures or results
  • Patients receiving any other anticancer or investigational drug therapy are excluded
  • Patients having taken valproic acid within 2 weeks prior to initiation of treatment are excluded
  • Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
  • Patients with a parabens allergy

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • National Cancer Institute Pediatric Oncology Branch

    Bethesda, Maryland, 20892

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Pediatric Brain Tumor Consortium

    Memphis, Tennessee, 38105

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Feasibility Study of Vorinostat (SAHA) Combined With Isotretinoin and Chemotherapy in Infants With Embryonal Tumors of the Central Nervous System

This pilot clinical trial studies the side effects and the best way to give vorinostat with isotretinoin and combination chemotherapy and to see how well they work in treating younger patients with embryonal tumors of the central nervous system. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as isotretinoin, vincristine sulfate, cisplatin, cyclophosphamide, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vorinostat with isotretinoin and combination chemotherapy may be an effective treatment for embryonal tumors of the central nervous system. A peripheral blood stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To investigate the feasibility of administering vorinostat (SAHA) and isotretinoin for three days prior and concomitant with cisplatin based chemotherapy over three courses of induction chemotherapy.

II. To describe the toxicity of administering vorinostat (SAHA) and isotretinoin for three days prior and concomitant with cisplatin based chemotherapy over three courses of induction chemotherapy.

III. To investigate prognostic values of histopathological classification and biological markers in the context of a feasibility study.

SECONDARY OBJECTIVES:

  1. To estimate the preliminary response rate of this approach in patients with measurable residual disease (primary site and/or metastatic sites).

II. To estimate disease specific progression-free and overall survival, in the context of a feasibility study.

III. To explore the predictive values of biological markers in cerebrospinal fluid (CSF), plasma, urine tumor material in the context of a feasibility study.

OUTLINE:

INDUCTION THERAPY: Patients receive vorinostat orally (PO) once daily (QD) and isotretinoin PO twice daily (BID) on days 1-4; vincristine sulfate intravenously (IV) on days 4, 11, and 18; cisplatin IV over 6 hours on day 4; cyclophosphamide IV over 1 hour on days 5-6; and etoposide phosphate IV over 1 hour on days 4-6. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo peripheral blood stem cell (PBSC) harvesting after each course.

CONSOLIDATION THERAPY: Within 6 weeks (10 weeks if patient is re-staged) after completion of induction therapy, patients receive carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1-2. Patients also receive autologous PBSC rescue infusion over 6 hours on day 4. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning 3 weeks later, patients with M0 non-desmoplastic medulloblastoma also undergo conformal radiotherapy* to the tumor bed.

NOTE: *Patients with supratentorial primary tumors or metastatic disease undergo radiotherapy at the discretion of treating physician.

MAINTENANCE THERAPY: Beginning 4 weeks after completion of radiotherapy or immediately after completion of consolidation therapy, patients receive vorinostat PO QD on days 1, 3, 5, 6, 8, 10, 12, and 13 and isotretinoin PO BID on days 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Being tested
3-Dimensional Conformal Radiation Therapy, Carboplatin, Cisplatin, Cyclophosphamide, Etoposide Phosphate
Medical subject headings
Medulloblastoma, Pinealoma

What participants receive

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

  • 3-Dimensional Conformal Radiation TherapyRadiation

    Also called 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT

    Undergo conformal radiation therapy

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Etoposide PhosphateDrug

    Also called Etopophos

    Given IV

  • IsotretinoinDrug

    Also called 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A Acid

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT

    Undergo PBSC

  • ThiotepaDrug

    Also called 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa

    Given IV

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given PO

Study groups in NCT00867178
Study groupRoleWhat they receive
Treatment (vorinostat, isotretinoin, chemotherapy)ExperimentalSee Detailed Description
Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Carboplatin; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Etoposide Phosphate; Drug: Isotretinoin; Other: Laboratory Biomarker Analysis; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Thiotepa; Drug: Vincristine Sulfate; Drug: Vorinostat

What is being measured

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

  1. Dose-limiting toxicity of proposed vorinostat

    Will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

    Measured: Up to 21 days

  2. Feasibility in terms of completing 3 courses of induction therapy

    Simon's two-stage optimal design will be used to assess feasibility.

    Measured: Within 98 days

  3. Prognostic value of histopathological classification of pediatric medulloblastoma

    Will be assessed by single-nucleotide polymorphism (SNP) analysis and gene expression analysis. Loss of heterozygosity (LOH) analysis and copy number analysis (CNA) will be performed using dChip SNP software (or R bioconductor package) for the paired samples. Association of copy number (and LOH) with gene expression data will be explored. Correlation analysis (Pearson or Spearman Correlation, as appropriate) will be used to estimate the strength of association between each SNP and expression signal. The multiplicity issue will be addressed through estimating the False Discovery Rate.

    Measured: Up to 5 years

Secondary outcomes (4)

  1. Response rate of this approach in patients with measurable residual disease (primary site and/or metastatic sites)

    Separate exact confidence interval estimates of objective responses following induction therapy will be constructed for patients with medulloblastomas (MBs) and PNETs. Cumulative incidence of objective responses as a function of course of therapy will also be provided.

    Measured: Up to 5 years

  2. Progression-free survival (PFS)

    Kaplan-Meier estimates of distributions of PFS will be provided. If sample sizes allow, these Kaplan-Meier estimates will be produced separately for patients with MBs and PNETs.

    Measured: Up to 5 years

  3. Overall survival (OS)

    Kaplan-Meier estimates of distributions of OS will be provided. If sample sizes allow, these Kaplan-Meier estimates will be produced separately for patients with MBs and PNETs.

    Measured: Up to 5 years

  4. Predictive values of biological markers in CSF, plasma and urine in the context of a feasibility study

    Frequency of the markers of interest present in this cohort will be provided and their associations with disease outcome will be explored. Similarly if sample size constraints make such analyses feasible, the associations between the markers of interest and clinical and demographic variables will be explored in a descriptive fashion.

    Measured: Up to 5 years

Timeline

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

  1. First posted23 Mar 2009 (estimated)
  2. Study start25 Feb 2009
  3. Primary completion9 Apr 2020
  4. Study completion22 Dec 2021

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
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00867178
Sponsor's protocol ID
NCI-2012-03167
Other IDs
NCI-2012-03167, PBTC-026, PBTC-026, PBTC-026, U01CA081457, UM1CA081457
Status last verified
Sep 2021
First submitted
20 Mar 2009
Last updated
13 Jan 2022
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 3-Dimensional Conformal Radiation Therapy, Carboplatin and Cisplatin in people with Medulloblastoma and Pineoblastoma, run by National Cancer Institute (NCI) at 15 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 12 inclusion and 6 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 13 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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?

Dose-limiting toxicity of proposed vorinostat (time frame: Up to 21 days). The study lists 3 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 NCT00867178.

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 13 Jan 2022.

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