Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma
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| ClinicalTrials.gov Identifier: NCT01236560 |
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Recruitment Status
:
Completed
First Posted
: November 8, 2010
Last Update Posted
: October 12, 2017
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Brain Stem Glioma Cerebral Astrocytoma Childhood Cerebellar Anaplastic Astrocytoma Childhood Cerebral Anaplastic Astrocytoma Childhood Spinal Cord Neoplasm Untreated Childhood Brain Stem Glioma Untreated Childhood Cerebral Astrocytoma | Biological: Bevacizumab Drug: Temozolomide Drug: Vorinostat | Phase 2 Phase 3 |
Show Detailed Description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 101 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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 |
| Actual Study Start Date : | November 15, 2010 |
| Actual Primary Completion Date : | September 27, 2016 |
| Actual Study Completion Date : | September 27, 2016 |
Resource links provided by the National Library of Medicine
Genetic and Rare Diseases Information Center resources:
Glioma
Anaplastic Astrocytoma
Childhood Brain Stem Glioma
Cerebral Astrocytoma, Childhood
Neuroepithelioma
U.S. FDA Resources
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Vorinostat
Given PO
Other Names:
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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.
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Drug: Temozolomide
Given PO
Other Names:
Drug: Vorinostat
Given PO
Other Names:
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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.
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Biological: Bevacizumab
Given IV
Other Names:
Drug: Vorinostat
Given PO
Other Names:
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Experimental: Arm IV (vorinostat and temozolomide)
Patients receive RT and temozolomide as in phase II, arm II.
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Drug: Temozolomide
Given PO
Other Names:
Drug: Vorinostat
Given PO
Other Names:
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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.
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Biological: Bevacizumab
Given IV
Other Names:
Drug: Temozolomide
Given PO
Other Names:
Drug: Vorinostat
Given PO
Other Names:
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Primary Outcome Measures
:
- 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 ]
- 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 ]
Secondary Outcome Measures
:
- Overall survival of patients in each treatment arm [ Time Frame: Up to 10 years ]
- Progression-free survival of patients in each treatment arm [ Time Frame: Up to 10 years ]
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| Ages Eligible for Study: | 3 Years to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Newly diagnosed high-grade glioma
- Anaplastic astrocytoma
- Glioblastomamultiforme
- Gliosarcoma
- Primary spinal cord malignant glioma allowed
- No oligodendroglioma oroligoastrocytoma
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Patient must have histological verification of diagnosis
- No M+ disease (defined as evidence of neuraxis dissemination)
- No positive CSF cytology
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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)
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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)
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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
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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
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More than 7 days since major surgical procedure and recovered
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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)
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- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01236560
Show 131 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Maryam Fouladi | Children's Oncology Group |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01236560 History of Changes |
| Other Study ID Numbers: |
NCI-2011-02616 NCI-2011-02616 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000688443 ACNS0822 ACNS0822 ( Other Identifier: Childrens Oncology Group ) ACNS0822 ( Other Identifier: CTEP ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | November 8, 2010 Key Record Dates |
| Last Update Posted: | October 12, 2017 |
| Last Verified: | October 2017 |
Additional relevant MeSH terms:
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Glioma Astrocytoma Spinal Cord Neoplasms Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms 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 Bevacizumab Temozolomide Vorinostat Dacarbazine Endothelial Growth Factors Antibodies Immunoglobulins Antibodies, Monoclonal Immunoglobulin G Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors |