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NCT01189266 · REGISTRY CONDITION SEARCH

Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
COMPLETED
Registry last update
2021-10-28

This phase I/II trial studies 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 diffuse intrinsic pontine glioma (a brainstem tumor). 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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Maximum Tolerated Dose (MTD) of Vorinostat

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outcome · POSTED

Event-Free Survival

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outcome · POSTED

Incidence of Toxicity During Chemoradiation Therapy

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outcome · POSTED

Incidence of Toxicity During Maintenance Therapy

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outcome · POSTED

Overall Survival

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outcome · POSTED

Change in H3 and H4 Acetylation Levels in PBMCs

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outcome · POSTED

Change in NHEJ Activity in PBMCs

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outcome · POSTED

Levels of DNA Repair Proteins in Paraffin-embedded Blocks, Measured Via Immunohistochemistry or Western Analysis

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons, are eligible without histologic confirmation; patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma; patients with juvenile pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible; patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician * Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 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 score * Patients must not have received any prior treatment except dexamethasone and/or surgery * Peripheral absolute neutrophil count (ANC) \>= 1000/uL * Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment) * Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows: * 0.8 mg/dL (3 to \< 6 years of age) * 1 mg/dL (6 to \< 10 years of age) * 1.2 mg/dL (10 to \< 13 years of age) * 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to \< 16 years of age) * 1.7 mg/dL (male) or 1.4 mg/dL (female) (\>= 16 years of age) * Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 110 U/L; for the purpose of this study, the ULN for SGPT (ALT) is 45 U/L * Serum albumin \>= 2 g/dL * Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants (with the exception of valproic acid) and seizures are well controlled * Patients must be able to swallow capsules or liquids; patients dependent on nasogastric (NG) tube feeding are not permitted to receive protocol therapy * Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date Exclusion Criteria: * Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method * Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment * Patients who are currently receiving another investigational drug are not eligible * Patients who are currently receiving other anti-cancer agents are not eligible * Patients must not currently be receiving enzyme inducing anticonvulsants * Patients on valproic acid must discontinue valproic acid for at least 2 weeks before starting protocol therapy * Patients receiving coumadin, heparin, low-molecular weight heparin, or any other anti-coagulants are not eligible for study entry * Patients receiving acetylsalicylic acid (ASA) (\> 81 mg/day), non-steroidal anti-inflammatory drugs, clopidogrel (Plavix), dipyridamole (Persantine), or any other drug that inhibits platelet function are not eligible for study entry * Patients who have an uncontrolled infection are not eligible * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
healthy Volunteers
false
maximum Age
21 Years
minimum Age
37 Months
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients in phase I received vorinostat at 180 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Radiation: 3-Dimensional Conformal Radiation Therapy
    2. Radiation: Intensity-Modulated Radiation Therapy
    3. Other: Laboratory Biomarker Analysis
    4. Drug: Vorinostat
    label
    Arm 1 Phase I Vorinostat 180 mg/m^2
    type
    EXPERIMENTAL
  2. description
    Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Radiation: 3-Dimensional Conformal Radiation Therapy
    2. Radiation: Intensity-Modulated Radiation Therapy
    3. Other: Laboratory Biomarker Analysis
    4. Drug: Vorinostat
    label
    Arm 2 Phase 1 Vorinostat 230 mg/m^2
    type
    EXPERIMENTAL
  3. description
    Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Radiation: 3-Dimensional Conformal Radiation Therapy
    2. Radiation: Intensity-Modulated Radiation Therapy
    3. Other: Laboratory Biomarker Analysis
    4. Drug: Vorinostat
    label
    Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm 1 Phase I Vorinostat 180 mg/m^2
    2. Arm 2 Phase 1 Vorinostat 230 mg/m^2
    3. Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
    description
    Undergo 3D conformal radiation therapy
    name
    3-Dimensional Conformal Radiation Therapy
    other Names
    1. 3-dimensional radiation therapy
    2. 3D Conformal
    3. 3D CONFORMAL RADIATION THERAPY
    4. 3D CRT
    5. 3D-CRT
    6. Conformal Therapy
    7. Radiation Conformal Therapy
    8. Radiation, 3D Conformal
    type
    RADIATION
  2. arm Group Labels
    1. Arm 1 Phase I Vorinostat 180 mg/m^2
    2. Arm 2 Phase 1 Vorinostat 230 mg/m^2
    3. Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
    description
    Undergo intensity-modulated radiation therapy
    name
    Intensity-Modulated Radiation Therapy
    other Names
    1. IMRT
    2. Intensity Modulated RT
    3. Intensity-Modulated Radiotherapy
    4. Radiation, Intensity-Modulated Radiotherapy
    type
    RADIATION
  3. arm Group Labels
    1. Arm 1 Phase I Vorinostat 180 mg/m^2
    2. Arm 2 Phase 1 Vorinostat 230 mg/m^2
    3. Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
    description
    Correlative studies
    name
    Laboratory Biomarker Analysis
    type
    OTHER
  4. arm Group Labels
    1. Arm 1 Phase I Vorinostat 180 mg/m^2
    2. Arm 2 Phase 1 Vorinostat 230 mg/m^2
    3. Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
    description
    Given PO
    name
    Vorinostat
    other Names
    1. L-001079038
    2. MSK-390
    3. SAHA
    4. Suberanilohydroxamic Acid
    5. Suberoylanilide Hydroxamic Acid
    6. Zolinza
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
79
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    The dose of vorinostat in mg/sqm/day to be administered with combination chemotherapy and radiation therapy
    measure
    Maximum Tolerated Dose (MTD) of Vorinostat
    time Frame
    Planned 7 weeks during chemoradiotherapy
  2. description
    Time from enrollment to disease progression, diagnosis of a second malignant neoplasm, death or last follow-up, whichever occurs first.
    measure
    Event-Free Survival
    time Frame
    2 years after study enrollment
  3. description
    Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
    measure
    Incidence of Toxicity During Chemoradiation Therapy
    time Frame
    Planned 7 weeks during chemoradiotherapy
  4. description
    Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
    measure
    Incidence of Toxicity During Maintenance Therapy
    time Frame
    Planned 12 months of maintenance with Vorinostat
secondary Outcomes
  1. description
    Time from enrollment to death or last follow-up, whichever occurs first.
    measure
    Overall Survival
    time Frame
    2 years after study enrollment
  2. description
    Degree of acetylation in peripheral blood monocytes will be divided into quartiles and coded as none, mild, moderation or marked.
    measure
    Change in H3 and H4 Acetylation Levels in PBMCs
    time Frame
    Baseline to up to 7 weeks
  3. description
    Descriptive statistics will be used to summarize the biological/laboratory measures and the changes in these measures across time-points.
    measure
    Change in NHEJ Activity in PBMCs
    time Frame
    Baseline to up to 7 weeks
  4. description
    For immunohistochemistry from tumor blocks, the intensity will be graded from 1 to 3; for Western analysis, a percentage of the intensity relative to the tumor with the highest level will be measured.
    measure
    Levels of DNA Repair Proteins in Paraffin-embedded Blocks, Measured Via Immunohistochemistry or Western Analysis
    time Frame
    Baseline
Full study description
brief Summary
This phase I/II trial studies 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 diffuse intrinsic pontine glioma (a brainstem tumor). 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.
detailed Description
PRIMARY OBJECTIVES: l. To estimate the maximum tolerated dose (MTD) or recommend a phase 2 dose of vorinostat given concurrently with radiation in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). II. To define and describe the toxicities of vorinostat given concurrently with radiation in children with newly diagnosed DIPG. III. To determine, in the context of this phase I/II trial, the anti-tumor activity of combining vorinostat with radiation, followed by maintenance vorinostat for twelve courses, in children with newly diagnosed DIPG, as measured by 12-month event-free survival (EFS) and overall survival (OS). IV. To determine the toxicities of vorinostat for 12 additional courses after completion of vorinostat and radiation. 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 radiation, and at the end of radiation. II. To measure histone deacetylase 2 (HDAC2) levels and assess histone acetylation in PBMCs before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of radiation. III. To quantify deoxyribonucleic acid (DNA) repair proteins from the NHEJ and homologous recombination repair (HHR) pathways in tumors by either Western analysis or immunohistochemistry, if paraffin-embedded tumor is available. OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study. Patients receive vorinostat orally (PO) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients undergo 3-dimensional (3D) conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. Patients then receive maintenance therapy comprising vorinostat PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.
Source references
Source notices and limitations
    Discovery and provenance
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      query disease state id
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    Preserved source evidence · Not medical advice