VEGF Trap in Treating Patients With Recurrent Malignant Gliomas That Did Not Respond to Temozolomide

NCT ID: NCT00369590

Last Updated: 2015-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2012-10-31

Brief Summary

This phase II trial is studying how well VEGF Trap works in treating patients with recurrent malignant or anaplastic gliomas that did not respond to temozolomide. VEGF Trap may stop the growth of malignant or anaplastic gliomas by blocking blood flow to the tumor.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the therapeutic efficacy of VEGF Trap in patients with temozolomide-resistant malignant gliomas at first recurrence as measured by 6-month progression-free survival (PFS).

II. Determine the safety profile of VEGF Trap in these patients.

SECONDARY OBJECTIVES:

I. Determine the efficacy of this regimen as measured by radiographic response, PFS, time to progression, and overall survival.

II. Characterize the single-dose and repeated-dose pharmacokinetic profiles of VEGF Trap in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (glioblastoma vs anaplastic glioma).

Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Conditions

Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All Study Patients

Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Other: pharmacological study; laboratory biomarker analysis.

Group Type: EXPERIMENTAL

ziv-aflibercept

Intervention Type: BIOLOGICAL

Given IV

pharmacological study

Intervention Type: OTHER

correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

correlative studies

Interventions

ziv-aflibercept

Given IV

Intervention Type: BIOLOGICAL

pharmacological study

correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

correlative studies

Intervention Type: OTHER

Other Intervention Names

aflibercept; vascular endothelial growth factor trap; VEGF Trap; Zaltrap

Eligibility Criteria

Inclusion Criteria

• International Normalized Ratio (INR) < = 1.5
• Platelet count => 100,000/mm³
• Hemoglobin => 10 g/dL (transfusion allowed)
• Serum glutamic oxaloacetic transaminase (SGOT)/Serum glutamic pyruvic transaminase (SGPT) < = 2 times upper limit of normal (ULN)
• Not pregnant or nursing
• Negative pregnancy test
• No previous Vascular endothelial growth factor (VEGF) Trap
• At least 4 weeks since chemotherapy, surgery, or open biopsy
• At least 2 weeks since vincristine
• At least 6 weeks since carmustine, lomustine, fotemustine, or radiation therapy
• At least 42 days since prior nitrosoureas
• At least 3 weeks since procarbazine
• No previous Gliadel wafers or bevacizumab
• Tumor did not respond to previous radiation therapy and temozolomide
• Karnofsky performance status (KPS) 60-100%
• Life expectancy = > 8 weeks
• White blood count (WBC) = >3,000/mm³
• Absolute neutrophil count = > 1,500/mm³
• Bilirubin < = 2 times ULN
• Creatinine < = 1.5 mg/dL OR creatinine clearance= > 60 mL/min
• Urine protein:creatinine ratio < = 1 OR 24-hour urine protein < = 500 mg/dL
• Fertile patients must use effective contraception prior to, during, and for = > 6 months after completion of study treatment
• No significant medical illnesses that, in the opinion of the investigator, cannot be adequately controlled with appropriate therapy or would preclude compliance with study treatment
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
• No history of any 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 = >3 years
• At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin [radiosensitizer does not count])
• At least 7 days since prior core biopsy
• At least 28 days since prior investigational agents
• No prior bevacizumab or vascular endothelial growth factor receptor inhibitors
• No concurrent full-dose anticoagulants (e.g., warfarin or low molecular-weight heparin)
• No clinically significant cardiovascular disease, including any of the following:

• Cerebrovascular accident within the past 6 months
• Uncontrolled hypertension, defined as blood pressure (BP) > 140/90 mm Hg or systolic BP > 180 mm Hg if diastolic BP < 90 mm Hg, on ≥ 2 repeated determinations on separate days within the past 3 months
• Myocardial infarction, coronary artery bypass graft (CABG), or unstable angina pectoris within the past 6 months
• New York Heart Association class III-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• Clinically significant peripheral vascular disease within the past 6 months
• Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
• No evidence of bleeding diathesis or coagulopathy
• No more than 1 prior chemotherapy regimen (initial treatment and treatment for 1 relapse)
• Surgical resection for relapsed disease with no anticancer therapy instituted for up to 12 weeks followed by another surgical resection is considered 1 relapse
• If prior therapy for a grade 3 glioma was given, surgical diagnosis of a high-grade glioma is considered the first relapse
• Prior surgical, interstitial brachytherapy, or stereotactic radiosurgery not considered prior therapy
• If prior therapy included interstitial brachytherapy or stereotactic radiosurgery, must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) scan, thallium scanning, Magnetic Resonance (MR) spectroscopy, or surgical documentation of disease
• Must show unequivocal radiographic evidence of tumor progression by MRI
• Recent resection of recurrent or progressive tumor allowed
• Residual disease not required
• Temozolomide-resistant recurrent glioblastoma is defined as tumor progression or tumor recurrence during or after treatment with temozolomide-based chemotherapy regimens
• Recovered from prior therapy
• No other disease that would obscure toxicity or dangerously alter drug metabolism
• No uncontrolled intercurrent illness, including, but not limited to, any of the following:

• Ongoing or active infection
• Psychiatric illness or social situations that would limit compliance with study requirements
• No serious or nonhealing wound, ulcer, or bone fracture
• No history of intracerebral or intratumoral hemorrhage
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No significant traumatic injury within the past 28 days
• At least 28 days since prior cytotoxic therapy
• Histologically confirmed diagnosis of 1 of the following:

• Intracranial glioblastoma or gliosarcoma
• Anaplastic astrocytoma
• Anaplastic oligodendroglioma
• Anaplastic mixed oligoastrocytoma
• Malignant astrocytoma not otherwise specified

• NOTE: If original histology was grade 3 glioma, subsequent histological diagnosis of 1 of these diseases is allowed provided no prior diagnosis of grade 2 glioma
• At least 20 unstained slides OR 1 tissue block available from original diagnostic biopsy/surgery or from biopsy/surgery at recurrence
• Patients presenting at the time of first recurrence or relapse, defined as progression after initial therapy (i.e., radiotherapy +/- chemotherapy if that was used as initial therapy) are eligible
• No other concurrent investigational drugs
• No other concurrent investigational drugs
• No concurrent cytotoxic or noncytotoxic therapy, including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy
• No concurrent major surgery
• No concurrent combination antiretroviral therapy for HIV-positive patients
• Concurrent anticonvulsant therapy allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John de Groot, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

University of California Los Angeles

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

M D Anderson Cancer Center

Houston, Texas, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

References

de Groot JF, Lamborn KR, Chang SM, Gilbert MR, Cloughesy TF, Aldape K, Yao J, Jackson EF, Lieberman F, Robins HI, Mehta MP, Lassman AB, Deangelis LM, Yung WK, Chen A, Prados MD, Wen PY. Phase II study of aflibercept in recurrent malignant glioma: a North American Brain Tumor Consortium study. J Clin Oncol. 2011 Jul 1;29(19):2689-95. doi: 10.1200/JCO.2010.34.1636. Epub 2011 May 23.

Reference Type: BACKGROUND

PMID: 21606416 (View on PubMed)

de Groot JF, Piao Y, Tran H, Gilbert M, Wu HK, Liu J, Bekele BN, Cloughesy T, Mehta M, Robins HI, Lassman A, DeAngelis L, Camphausen K, Chen A, Yung WK, Prados M, Wen PY, Heymach JV. Myeloid biomarkers associated with glioblastoma response to anti-VEGF therapy with aflibercept. Clin Cancer Res. 2011 Jul 15;17(14):4872-81. doi: 10.1158/1078-0432.CCR-11-0271. Epub 2011 Jun 1.

Reference Type: DERIVED

PMID: 21632852 (View on PubMed)

Other Identifiers

NCI-2009-00677

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000495275

Identifier Type: -

Identifier Source: secondary_id

NABTC06-01

Identifier Type: OTHER

Identifier Source: secondary_id

NABTC-06-01

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA062399

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00677

Identifier Type: -

Identifier Source: org_study_id