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Phase II Single Arm Trial of VEGF Trap in Patients With Recurrent Temozolomide-Resistant Malignant Gliomas

Phase 2
18 Years
Open (Enrolling)
Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Gliosarcoma, Adult Mixed Glioma, Recurrent Adult Brain Tumor

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Trial Information

Phase II Single Arm Trial of VEGF Trap in Patients With Recurrent Temozolomide-Resistant Malignant Gliomas


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

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


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.

Inclusion Criteria:

- INR < = 1.5

- Platelet count => 100,000/mm³

- Hemoglobin => 10 g/dL (transfusion allowed)

- SGOT/SGPT < = 2 times upper limit of normal (ULN)

- Not pregnant or nursing

- Negative pregnancy test

- No previous 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 60-100%

- Life expectancy = > 8 weeks

- 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

- 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

- 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, 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

- 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

- Ongoing or active infection

- Psychiatric illness or social situations that would limit compliance with study

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS) at 6 months

Outcome Description:

This design yields 85% power to detect a true 30% 6-month PFS rate, while maintaining .91 probability of rejecting for a true 15% 6-month PFS rate.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

John de Groot

Investigator Role:

Principal Investigator

Investigator Affiliation:

North American Brain Tumor Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

August 2006

Completion Date:

Related Keywords:

  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Oligodendroglioma
  • Adult Giant Cell Glioblastoma
  • Adult Gliosarcoma
  • Adult Mixed Glioma
  • Recurrent Adult Brain Tumor
  • Astrocytoma
  • Brain Neoplasms
  • Glioblastoma
  • Glioma
  • Oligodendroglioma
  • Gliosarcoma



North American Brain Tumor Consortium Watertown, Massachusetts  02472