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

August 25, 2010
August 4, 2014
August 2010
November 2020   (final data collection date for primary outcome measure)
  • 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 ]
  • Maximum-tolerated dose [ Designated as safety issue: Yes ]
  • Event-free survival [ Designated as safety issue: No ]
  • Toxicities [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01189266 on ClinicalTrials.gov Archive Site
Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Vorinostat and Radiation Therapy Followed By Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Pontine Glioma
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)

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.

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Childhood Mixed Glioma
  • Untreated Childhood Brain Stem Glioma
  • 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
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.
Interventions:
  • Drug: vorinostat
  • Radiation: 3-dimensional conformal radiation therapy
  • Radiation: intensity-modulated radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
80
Not Provided
November 2020   (final data collection date for primary outcome measure)

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
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada
 
NCT01189266
NCI-2011-02600, NCI-2011-02600, CDR0000683459, COG-ACNS0927, ACNS0927, ACNS0927, U10CA098543, U01CA097452
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Jack Su Children's Oncology Group
National Cancer Institute (NCI)
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP