Aflibercept, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed or Recurrent Glioblastoma Multiforme, Gliosarcoma, or Other Malignant Glioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00650923
First received: April 1, 2008
Last updated: May 29, 2014
Last verified: April 2014
  Purpose

This phase I trial is studying the side effects and best dose of aflibercept when given together with radiation therapy and temozolomide in treating patients with newly diagnosed or recurrent glioblastoma multiforme, gliosarcoma, or other malignant glioma. Aflibercept may stop the growth of tumor cells by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving aflibercept together with radiation therapy and temozolomide may kill more tumor cells.


Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Adult Mixed Glioma
Recurrent Adult Brain Tumor
Drug: ziv-aflibercept
Procedure: radiation therapy
Drug: temozolomide
Procedure: pharmacological study
Procedure: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Aflibercept (VEGF Trap) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients With Malignant Glioma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose of aflibercept defined as the dose at which fewer than one-third of patients experience DLT based on the CTC severity grading [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy in terms of antitumor activity based on clinical, radiographic, and biologic assessments [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.

  • Plasma aflibercept (VEGF Trap) concentrations and PK parameters such as Cmax, Tmax, area under the plasma concentration-time curve (AUCo-t and AUC), clearance (CL), apparent volume of distribution at steady state (Vdss), and terminal half-life (t1/2) [ Time Frame: Baseline and days 15, 16, 22, 29, 57, 85 of course 1 for patients in Arm I; baseline and days 2, 8, 15, 43, 71 of course 1 for patients in Arms 2 and 3 ] [ Designated as safety issue: No ]
    Will be determined using non-compartmental methods. Dose proportionality in PK parameters will be determined by performing a one-way analysis of variance (ANOVA) on dose-normalized parameters. In addition, summary tables depicting individual patient concentrations and individual and mean PK parameters will be provided.


Enrollment: 61
Study Start Date: July 2008
Study Completion Date: December 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
See Detailed Description
Drug: ziv-aflibercept
Given IV
Other Names:
  • aflibercept
  • vascular endothelial growth factor trap
  • VEGF Trap
  • Zaltrap
Procedure: radiation therapy
Undergo RT
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: temozolomide
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Procedure: pharmacological study
Correlative studies
Other Name: pharmacological studies
Procedure: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Creatinine < = 1.5 mg/dL or creatinine clearance = > 60 mL/min
  • At least 28 days since prior major surgery or open biopsy
  • INR < = 1.5
  • Not pregnant or nursing
  • Negative pregnancy test
  • Karnofsky performance status 60-100%
  • SGOT and SGPT < 2 times upper limit of normal (ULN)
  • Bilirubin < 2 times ULN
  • Life expectancy = > 12 weeks
  • WBC = > 3,000/μL
  • ANC= > 1,500/mm³
  • Platelet count = > 100,000/mm³
  • Hemoglobin = > 10 g/dL (transfusion allowed)
  • At least 21 days since prior radiotherapy (groups 2 and 3)
  • No prior Gliadel® wafers
  • No concurrent major surgery
  • Fertile patients must use effective contraception prior to, during, and for at least 6 months after completion of study treatment
  • At least 28 days since prior significant traumatic injury No evidence of bleeding diathesis or coagulopathy
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No history of other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years
  • No history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess gastrointestinal bleeding or diverticulitis within the past 6 months
  • No prior cranial radiotherapy (group 1 only)
  • No prior aflibercept
  • No prior treatment for brain tumors, except concurrent radiotherapy and temozolomide or 2 or fewer 28-day courses of adjuvant temozolomide (groups 2 and 3)
  • No prior or concurrent cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors (group 1 only)
  • No concurrent major surgery
  • No known hypersensitivity to CHO cell products or other recombinant human antibodies
  • No history of hypersensitivity to a recombinant protein whereby reaction occurs during or immediately after infusion
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to other study agents
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness or social situation that would limit compliance with study requirements
  • No clinically significant cardiovascular disease within the past 6 months, including any of the following:

History of ischemic or hemorrhagic stroke

  • Myocardial infarction, coronary artery bypass graft, or unstable angina
  • New York Heart Association class III-IV congestive heart failure, serious cardiac arrhythmia requiring medication, or unstable angina pectoris
  • Clinically significant peripheral vascular disease
  • Pulmonary embolism, deep vein thrombosis, or other thromboembolic event
  • No disease that will obscure toxicity or dangerously alter drug metabolism
  • Recovered from all prior therapy
  • More than 28 days since prior and no concurrent investigational agents
  • More than 7 days since prior core biopsy
  • At least 23 days since prior temozolomide (groups 2 and 3)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent full-dose anticoagulants (e.g., warfarin or low molecular-weight heparin)
  • Prophylactic doses allowed
  • No concurrent routine prophylactic use of filgrastim (G-CSF)
  • No other concurrent anticancer therapy (including chemotherapy, radiotherapy, hormonal treatment, or immunotherapy)
  • Concurrent enzyme-inducing antiepileptic drugs (EIAED) or non-EIAED allowed
  • Urine protein:creatinine ratio < = 1 or 24-hour urine protein < = 500 mg
  • No significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate therapy
  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: NCT00650923

Locations
United States, California
University of California at Los Angeles (UCLA )
Los Angeles, California, United States, 90095
UCSF-Mount Zion
San Francisco, California, United States, 94115
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Maryland
Adult Brain Tumor Consortium
Baltimore, Maryland, United States, 21231-1000
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Charlestown, Massachusetts, United States, 02129
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Patrick Wen National Cancer Institute (NCI)
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00650923     History of Changes
Other Study ID Numbers: NCI-2009-00678, NCI-2009-00678, CDR0000590174, NABTC-07-01, NABTC07-01, NABTC-07-01, U01CA137443
Study First Received: April 1, 2008
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Glioma
Gliosarcoma
Oligodendroglioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Endothelial Growth Factors
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014