Vorinostat and Radiation Therapy Followed By Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Pontine Glioma

This study has suspended participant recruitment.
(Temporarily Closed to Accrual)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01189266
First received: August 25, 2010
Last updated: August 4, 2014
Last verified: March 2014
  Purpose

This phase I/II trial is studying the side effects and best dose of vorinostat and to see how well it works when given together with radiation therapy followed by maintenance therapy with vorinostat in treating younger patients with newly diagnosed pontine gliomas. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vorinostat together with radiation therapy may kill more tumor cells.


Condition Intervention Phase
Childhood Mixed Glioma
Untreated Childhood Brain Stem Glioma
Drug: vorinostat
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) and Local Irradiation, Followed by Maintenance SAHA in Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas (DIPG)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of vorinostat in combination with radiation therapy determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Event-free survival [ Time Frame: From study enrollment to disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: August 2010
Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive vorinostat orally or IV on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients undergo 3D-conformal or intensity-modulated radiotherapy 5 days per week for 6 weeks. Patients then receive maintenance therapy comprising oral vorinostat on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: vorinostat
Given PO or IV
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Radiation: 3-dimensional conformal radiation therapy
Undergo radiation
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Radiation: intensity-modulated radiation therapy
Undergo radiation
Other Name: IMRT

Detailed Description:

PRIMARY OBJECTIVES:

l. To estimate the maximum-tolerated dose (MTD) or recommend a phase II dose of vorinostat given concurrently with radiotherapy in pediatric patients with newly diagnosed intrinsic pontine gliomas.

II. To define and describe the toxicities of vorinostat given concurrently with radiotherapy in these patients.

III. To determine, in the context of a this phase I/II trial, the antitumor activity of combining vorinostat with radiotherapy followed by maintenance vorinostat for 12 courses in these patients, as measured by 12-month event-free survival and overall survival.

IV. To determine the toxicities of vorinostat for 12 additional courses after completion of concurrent vorinostat and radiotherapy.

SECONDARY OBJECTIVES:

I. To measure non-homologous end-joining (NHEJ) activity in peripheral blood mononuclear cells (PBMCs) before treatment, at 2 weeks after starting vorinostat and radiotherapy, and at the end of radiotherapy.

II. To measure HDAC2 levels and assess histone acetylation in PBMCs before treatment, at 2 weeks after starting vorinostat and radiotherapy, and at the end of radiotherapy.

III. To quantify DNA repair proteins from the NHEJ and homologous recombination repair pathways in tumors by either Western analysis or IHC, if paraffin-embedded tumor is available.

OUTLINE: This is a multicenter, phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients receive vorinostat orally or IV on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients undergo 3D-conformal or intensity-modulated radiotherapy 5 days per week for 6 weeks. Patients then receive maintenance therapy comprising oral vorinostat on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Blood and tumor samples may be collected periodically for correlative studies.

After completion of study treatment, patients are followed up for up to 5 years.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed diffuse intrinsic pontine gliomas (defined as tumors with a pontine epicenter and diffuse involvement of ≥ 2/3 of the pons)

    • Patients with brainstem tumors that do not meet these criteria or are not considered to be typical intrinsic pontine gliomas are eligible provided their tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma
    • No patients with juvenile pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia
    • No patients with disseminated disease (MRI of the spine must be performed if disseminated disease is suspected by the treating physician)
  • Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) or Lansky PS 50-100% (for patients ≤ 16 years of age)

    • Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance status
  • ANC ≥ 1,000/uL
  • Platelet count ≥ 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within the past 7 days)
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age/gender as follows:

    • ≤ 0.8 mg/dL (for patients 3 to < 6 years of age)
    • ≤ 1 mg/dL (for patients 6 to < 10 years of age)
    • ≤ 1.2 mg/dL (for patients 10 to < 13 years of age)
    • ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
    • ≤ 1.5 mg/dL (for male patients 13 to < 16 years of age)
    • ≤ 1.7 mg/dL (for male patients ≥ 16 years of age)
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit of normal (ULN) for age
  • ALT ≤ 110 U/L (for the purpose of this study, the ULN for ALT is 45 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 liquids
  • Not dependent on NG tube feeding
  • Patients with seizure disorder are eligible provided that they are not on enzyme-inducing anticonvulsants and seizures are well controlled
  • No uncontrolled infection
  • No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
  • No prior treatment except for dexamethasone and/or surgery
  • At least 2 weeks since prior valproic acid
  • More than 7 days since prior growth factors that support platelet or white cell number or function
  • No other concurrent investigational drugs
  • No other concurrent anticancer agents (including chemotherapy, immunotherapy, or biologic therapy)
  • No concurrent coumadin, heparin, low-molecular weight heparin, or any other anticoagulants
  • No concurrent aspirin (> 81 mg/day), NSAIDs, clopidogrel (Plavix), dipyridamole (Persantine), or any other drug that inhibits platelet function
  • No concurrent enzyme-inducing anticonvulsants
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01189266

  Show 176 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Jack Su Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01189266     History of Changes
Other Study ID Numbers: NCI-2011-02600, NCI-2011-02600, CDR0000683459, COG-ACNS0927, ACNS0927, ACNS0927, U10CA098543, U01CA097452
Study First Received: August 25, 2010
Last Updated: August 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Vorinostat
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 25, 2014