Trial record 1 of 1 for:    NCT01236560
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Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01236560
First received: November 5, 2010
Last updated: August 22, 2014
Last verified: June 2014

November 5, 2010
August 22, 2014
November 2010
March 2019   (final data collection date for primary outcome measure)
  • Maximum tolerated dose (MTD) of vorinostat when given concurrently with radiation therapy determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) (feasability study) [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
  • Event-free survival of patients in each treatment arm, defined as time to first occurrence of disease progression, relapse, second malignant neoplasm, or death from any cause [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Dose-limiting toxicity of vorinostat when given with radiotherapy (feasibility study) [ Designated as safety issue: Yes ]
  • Toxicity of vorinostat, bevacizumab, or temozolomide when given in combination with radiotherapy [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01236560 on ClinicalTrials.gov Archive Site
  • Overall survival of patients in each treatment arm [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Progression-free survival of patients in each treatment arm [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Event-free survival of patients in each treatment arm [ Designated as safety issue: No ]
  • Overall survival of patients in each treatment arm [ Designated as safety issue: No ]
  • Progression-free survival of patients in each treatment arm [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma
A Randomized Phase II/III Study of Vorinostat and Local Irradiation OR Temozolomide and Local Irradiation OR Bevacizumab and Local Irradiation Followed by Maintenance Bevacizumab and Temozolomide in Children With Newly Diagnosed High-Grade Gliomas

This randomized phase II/III trial is studying vorinostat, temozolomide, or bevacizumab to see how well they work compared with each other when given together with radiation therapy followed by bevacizumab and temozolomide in treating young patients with newly diagnosed high-grade glioma. 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. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving vorinostat is more effective then temozolomide or bevacizumab when given together with radiation therapy in treating glioma.

PRIMARY OBJECTIVES:

I. To identify the dose of vorinostat that is feasible when given in combination with radiotherapy (RT) in patients with newly diagnosed high-grade gliomas (HGG). II. To compare 1-year event-free survival of patients with newly diagnosed HGG treated with vorinostat (using MTD) versus bevacizumab versus temozolomide when given in combination with RT followed by maintenance therapy with bevacizumab and temozolomide. (Phase II) III. To compare the event-free survival of patients with newly diagnosed HGG treated with the superior chemoradiotherapy (from phase II portion) versus temozolomide given in combination with RT followed by maintenance chemotherapy with bevacizumab and temozolomide. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate the anti-tumor activity, as measured by event-free survival (EFS), progression-free survival (PFS), and overall survival (OS), of patients with newly diagnosed HGG treated with vorinostat, bevacizumab, or temozolomide when given in combination with RT followed by maintenance chemotherapy with bevacizumab and temozolomide. II. To define and evaluate the toxicities of each of the treatment arms of the study.

III. To conduct gene expression profiling and SNP arrays in patients with newly diagnosed HGG.

IV. To assess telomerase activity, hTert expression, and telomere length in patients with newly diagnosed HGG. V. To document changes in perfusion and diffusion using MR imaging at baseline, prior to, during (prior to course 3), and after maintenance therapy with bevacizumab and temozolomide.

VI. To correlate functional changes in tumor with responses to bevacizumab treatment using MR diffusion/perfusion imaging. VII. To correlate the results of the bevacizumab biology studies in serum or tumor with EFS.

VIII. To explore the prognostic significance of MGMT status for patients newly diagnosed with HGG treated with combined surgery, radiation, chemotherapy, and anti-angiogenic therapy.

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

FEASIBILITY STUDY: Patients undergo 3-D conformal radiotherapy (RT) or intensity-modulated RT 5 days a week for 6 weeks. Patients also receive vorinostat orally (PO) once daily on days 1-5. Courses repeat every week for 6 weeks in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and temozolomide PO on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

PHASE II STUDY: Patients are stratified according to extent of resection (near total resection or gross total resection vs other) and histology (glioblastoma multiforme vs other). Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients undergo RT 5 days a week for 6 weeks and receive vorinostat at the maximum-tolerated dose determined in the feasibility study.

ARM II: Patients undergo RT as in arm I and receive temozolomide PO once daily for 42 days beginning on day 5 of RT.

ARM III: Patients undergo RT as in arm I and receive bevacizumab IV over 30-90 minutes on days 22 and 36. Patients in all arms receive maintenance therapy as in the feasibility study.

PHASE III study: Patients are randomized to 1 of 2 treatment arms.

ARM IV: Patients receive RT and temozolomide as in phase II, arm II.

ARM V: Patients receive treatment as in phase II, arm I or phase II, arm III, whichever was established as the superior chemoradiotherapy arm in phase II. Patients in all arms receive maintenance therapy as in the feasibility study. Some patients undergo blood and tumor tissue sample (from surgery) collection for telomerase activity, hTert expression, telomere length, and gene expression profiling and SNP arrays analysis.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Childhood High-grade Cerebellar Astrocytoma
  • Childhood High-grade Cerebral Astrocytoma
  • Childhood Spinal Cord Neoplasm
  • Untreated Childhood Brain Stem Glioma
  • Untreated Childhood Cerebral Astrocytoma
  • Drug: vorinostat
    Given PO
    Other Names:
    • L-001079038
    • SAHA
    • suberoylanilide hydroxamic acid
    • Zolinza
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Drug: temozolomide
    Given PO
    Other Names:
    • SCH 52365
    • Temodal
    • Temodar
    • TMZ
  • Experimental: Arm I (vorinostat)
    Patients undergo RT 5 days a week for 6 weeks and receive vorinostat at the maximum-tolerated dose determined in the feasibility study.
    Intervention: Drug: vorinostat
  • Experimental: Arm II (vorinostat and temozolomide)
    Patients undergo RT as in arm I and receive temozolomide PO once daily for 42 days beginning on day 5 of RT.
    Interventions:
    • Drug: vorinostat
    • Drug: temozolomide
  • Experimental: Arm III (vorinostat and bevacizumab)
    Patients undergo RT as in arm I and receive bevacizumab IV over 30-90 minutes on days 22 and 36.
    Interventions:
    • Drug: vorinostat
    • Biological: bevacizumab
  • Experimental: Arm IV (vorinostat and temozolomide)
    Patients receive RT and temozolomide as in phase II, arm II.
    Interventions:
    • Drug: vorinostat
    • Drug: temozolomide
  • Experimental: Arm V (vorinostat, bevacizumab, temozolomide)
    Patients receive treatment as in phase II, arm I or phase II, arm III, whichever was established as the superior chemoradiotherapy arm in phase II.
    Interventions:
    • Drug: vorinostat
    • Biological: bevacizumab
    • Drug: temozolomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
268
Not Provided
March 2019   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Newly diagnosed high-grade glioma

    • Anaplastic astrocytoma
    • Glioblastomamultiforme
    • Gliosarcoma
    • Primary spinal cord malignant glioma allowed
    • No oligodendroglioma oroligoastrocytoma
  • Patient must have histological verification of diagnosis

    • No M+ disease (defined as evidence of neuraxis dissemination)
    • No positive CSF cytology
  • ECOG performance status (PS) 0-2

    • Karnofsky PS 50-100% (patients > 16 years of age)
    • Lansky PS 50-100% (patients ≤ 16 years of age)
  • ANC ≥ 1,000/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 8.0 mg/dL (transfusion independent)
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:

    • 0.4 mg/dL (1 month to < 6 months of age)
    • 0.5 mg/dL (6 months to < 1 year of age)
    • 0.6 mg/dL (1 to < 2 years of age)
    • 0.8 mg/dL (2 to < 6 years of age)
    • 1.0 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)
  • Proteinuria < 2+ OR urine; protein ratio (UPC) ≤ 0.5

    • If UPC > 0.5, a 24-hour urine protein should be obtained and level should be < 1,000 mg of protein
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT < 2.5 times ULN
  • Serum albumin ≥ 2 g/dL
  • PT INR ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during all study therapy and for ≥ 6 months after completion of bevacizumab
  • Hypertension well controlled (≤ 95^th percentile for age and height if patient is ≤ 17years) by stable doses of medication allowed

    • For patients > 17 years, systolic blood pressure (BP) ≤ 150 mm Hg or diastolic BP ≤ 100 mm Hg)
  • Seizure disorder allowed provided patient is well-controlled and on nonenzyme-inducing anticonvulsants
  • No history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, ≥ grade 2 heart failure, or serious and inadequately controlled cardiac arrhythmia
  • No known bleeding diathesis or coagulopathy
  • No prior arterial thromboembolic events, including transient ischemic attacks orcerebrovascular accidents
  • No prior diagnosis of a deep venous thrombosis, including pulmonary embolism, and no known thrombophilic condition (e.g., protein S, protein C, antithrombin III deficiency, Factor V Leiden or Factor II G202`0A mutation, homocysteinemia, or antiphospholipid antibody syndrome)
  • No history of an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No serious or non-healing wound, ulcer, or bone fracture
  • No evidence of significant postoperative intracranial hemorrhage, defined as > 1 cm of blood on postoperative MRI scan (potentially in addition to the postoperative scan) obtained within the past 14days
  • No history of allergic reaction to Chinese hamster ovary cell products or other recombinanthuman antibodies
  • No more than 31 days since definitive surgery
  • Must not have received any prior chemotherapy, radiotherapy, immunotherapy, or bone marrow transplant
  • More than 7 days since major surgical procedure and recovered

    • For patients scheduled to receive bevacizumab:

      • More than 28 days since major procedure
      • More than 14 days since intermediate procedure
      • More than 7 days since minor procedure (lumbar picture or placement of PICC lines are not considered minor procedures)
  • No other current anti-cancer agents
  • No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase activity
  • No concurrent enzyme inducing anticonvulsants
  • No concurrent HDAC inhibitors (e.g., valproic acid)
  • No concurrent anticoagulants including systemic thrombolytic agents, heparin, low molecular weight heparins, or warfarin except as required to maintain patency of pre-existing permanent vascular catheters or for prevention of thrombosis in the post-operative period
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01236560
NCI-2011-02616, NCI-2011-02616, CDR0000688443, ACNS0822, ACNS0822, U10CA098543
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Maryam Fouladi Children's Oncology Group
National Cancer Institute (NCI)
June 2014

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