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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00650923
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Cancer Institute (NCI)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Patrick Wen
Principal Investigator Affiliation National Cancer Institute (NCI)
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

NIH
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Mixed Glioma, Recurrent Adult Brain Tumor
Additional Details

PRIMARY OBJECTIVES:

  • I. To define the maximum tolerated dose (MTD) of aflibercept (VEGF Trap) with radiotherapy (RT) and concurrent temozolomide (TMZ) when administered in patients with newly-diagnosed glioblastoma (GBM) or gliosarcoma.
  • II. To define the MTD of aflibercept with adjuvant TMZ administered at 150mg/m2once daily for 5 days every 28 days in patients with stable or recurrent malignant glioma (MG) after RT.
  • III. To define the MTD of aflibercept with adjuvant TMZ administered at 100 mg/m2 once daily for 21 days every 28 days in patients with stable or recurrent MG after RT.
  • IV. To characterize the safety profile of aflibercept in combination with RT and concomitant TMZ in patients with newly-diagnosed GBM.
  • V. To characterize the safety profile of aflibercept in combination with adjuvant TMZ in patients with stable or recurrent MG after RT.
SECONDARY OBJECTIVE:
  • I. To characterize the pharmacokinetic profiles of free and bound aflibercept and TMZ in these patients.
OUTLINE: This is a multicenter, dose-escalation study of aflibercept. Patients are assigned to 1 of 3 treatment groups according to prior treatment and diagnosis. Group 1 (newly diagnosed glioblastoma multiforme or gliosarcoma): Patients undergo involved field partial brain radiotherapy (RT) once daily, 5 days a week (total of 30 fractions) and receive concurrent oral temozolomide (TMZ) once daily for 6 weeks. Beginning 2 weeks after the initiation of RT patients also receive aflibercept IV over 1 hour on days 1 and 15 and continue until the end of RT. Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral TMZ once daily on days 1-5. Treatment with adjuvant TMZ repeats every 28 days for up to 12 courses. Group 2 (stable or recurrent malignant glioma): Patients undergo radiotherapy as in group 1. Patients receive oral TMZ on days 1-5. Treatment repeats every 28 days for up to 12* courses. Patients also receive aflibercept IV over 1 hour on days 1 and 15 beginning on the first day of TMZ treatment. [Note: *The 12 course maximum includes adjuvant TMZ courses administered prior to enrollment.] Group 3 (stable or recurrent malignant glioma): Patients undergo radiotherapy as in group 1. Patients receive oral TMZ on days 1-5. Treatment repeats every 21 days for up to 12* courses. Patients also receive aflibercept IV over 1 hour on days 1 and 15 beginning on the first day of TMZ treatment. [Note: *The 12 course maximum includes adjuvant TMZ courses administered prior to enrollment.] In all groups, treatment continues in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for analysis of pharmacokinetics by ELISA. Tumor biomarkers and plasma angiogenic peptides are analyzed for correlation with response, and tumor MGMT promoter methylation status is determined using methylation-specific PCR. After completion of study treatment, patients are followed every 3 months.

Arms & Interventions

Arms

Experimental: Arm 1

See Detailed Description

Interventions

Drug: - ziv-aflibercept

Given IV

Procedure: - radiation therapy

Undergo RT

Drug: - temozolomide

Given PO

Procedure: - pharmacological study

Correlative studies

Procedure: - laboratory biomarker analysis

Correlative studies

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Los Angeles, California

Status

Address

University of California at Los Angeles (UCLA )

Los Angeles, California, 90095

UCSF-Mount Zion, San Francisco, California

Status

Address

UCSF-Mount Zion

San Francisco, California, 94115

San Francisco, California

Status

Address

University of California San Francisco Medical Center-Parnassus

San Francisco, California, 94143

Adult Brain Tumor Consortium, Baltimore, Maryland

Status

Address

Adult Brain Tumor Consortium

Baltimore, Maryland, 21231-1000

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115

Massachusetts General Hospital, Charlestown, Massachusetts

Status

Address

Massachusetts General Hospital

Charlestown, Massachusetts, 02129

Memorial Sloan-Kettering Cancer Center, New York, New York

Status

Address

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065

University of Pittsburgh, Pittsburgh, Pennsylvania

Status

Address

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232

M D Anderson Cancer Center, Houston, Texas

Status

Address

M D Anderson Cancer Center

Houston, Texas, 77030