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: July 18, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
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
Biological: bevacizumab
Drug: temozolomide
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 268
Study Start Date: November 2010
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
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.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Drug: temozolomide
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
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.
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
Experimental: Arm IV (vorinostat and temozolomide)
Patients receive RT and temozolomide as in phase II, arm II.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Drug: temozolomide
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
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.
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

  Show Detailed Description

  Eligibility

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

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
  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: NCT01236560

  Show 129 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Maryam Fouladi Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01236560     History of Changes
Other Study ID Numbers: NCI-2011-02616, NCI-2011-02616, CDR0000688443, ACNS0822, ACNS0822, U10CA098543
Study First Received: November 5, 2010
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Neoplasms
Glioma
Spinal Cord Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Antibodies
Antibodies, Monoclonal
Temozolomide
Dacarbazine
Vorinostat
Bevacizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014