Clinical trial NCT00369590: VEGF Trap in Treating Patients With Recurrent Malignant Gliomas That Did Not Respond to Temozolomide
Official title: Phase II Single Arm Trial of VEGF Trap in Patients With Recurrent Temozolomide-Resistant Malignant Gliomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-08-29
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free Survival (PFS) at 6 Months
timeFrame: 6 months
measure: Safety Profile - Toxicities
timeFrame: Start to End of treatment 39 cycles or 1yr 7.5months (78 weeks)
measure: Safety Profile - Events That Discontinued Treatment
timeFrame: Approximately 1 year (start of treatment - end of treatment)
Secondary outcomes:
measure: Response Rate Associated With VEGF Trap Therapy Defined as Proportions of Patients Experiencing Complete or Partial Response
timeFrame: Up to 2 years
measure: Progression Free Survival (PFS) Rate for Subjects With Radiographic Response
timeFrame: up to 3 years
measure: Overall Survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: M.D. Anderson Cancer Center
name: John de Groot, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.