Eligibility Criteria

NABTC07-01: VEGF-Trap

Eligibility Criteria

Inclusion Criteria:

  1. Patients with histologically proven intracranial GBM or gliosarcoma (GS) will be eligible for this protocol.  For Arms 2 and 3, patients with AGs, including AA, anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma not otherwise specified (NOS) will also be eligible (See Section 4.36 of the protocol).
  2. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.  Patients must have signed an authorization for the release of their protected health information.  Patients must be registered in the ABTC COO database prior to treatment with study drug.
  3. Patients must be > 18 years old.  Because aflibercept (VEGF Trap) interferes with growth plate maturation in animals, this agent may be inappropriate for use in patients <18 years of age. For this reason and because no dosing or AE data are available on the use of aflibercept (VEGF Trap) in children, patients <18 years of age are excluded from this study but may be eligible for future pediatric single-agent trials, if applicable.
  4. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days.  If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required.  The same type of scan, i.e., MRI or CT, must be used throughout the period of protocol treatment for tumor measurement.  The use of MRI rather than CT is preferred.
  5. Patients must have a life expectancy of > 12 weeks.
  6. Patients must have a Karnofsky performance status of > 60 (see Appendix 18.2).
  7. Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT, SPGT and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.5 mg/dL or creatinine clearance > 60 cc/min/1.73 m2) before starting therapy.  These tests must be performed within 14 days prior to registration.  Eligibility level for hemoglobin may be reached by transfusion.
  8. Urine protein:creatinine ratio (UPCR) must be ≤ 1.  Subjects with UPCR > 1 will still be eligible if 24-hour urine protein is < 500 mg.
  9. Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while enrolled in the study.
  10. Although clinical data are lacking on the immediate or long-term effects of aflibercept (VEGF Trap) on the developing human fetus, the agent is teratogenic and negatively affects fetal development in animal models.  For this reason and because antiangiogenic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after completion of aflibercept (VEGF Trap) therapy.
  11. Women of childbearing potential must have a negative β-HCG pregnancy test documented within 14 days prior to registration.  Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.


Exclusion Criteria
 

  1. Patients must not have received prior Gliadel wafers.
  2. Patients must not have received any investigational agents within 28 days prior to commencing study treatment.
  3. Patients must not have any 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 this therapy.
  4. Patients with known hypersensitivity to CHO cell products or other recombinant human antibodies, and patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in the study.  A history of hypersensitivity to a recombinant protein that occurs during or immediately after infusion might include symptoms such as: dizziness, faintness, diaphoresis, pruritus, shortness of breath; GI symptoms including nausea, vomiting, diarrhea, and abdominal cramping; rash including hives or urticaria.
  5. Patients with a history of any other cancer (except non-melanoma 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 are ineligible.
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  7. Serious or non-healing wound, ulcer, or bone fracture.
  8. Patients who have a pre-operative MRI that demonstrates significant intratumoral or peritumoral hemorrhage or have a post-operative MRI that demonstrates a large amount of peri-operative parenchymal hemorrhage are not eligible.  Patients may have postoperative intracavitary blood.
  9. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess gastrointestinal bleeding, or diverticulitis within 6 months of treatment.
  10. Patients with the following invasive procedures:
    1. Major surgical procedure, open biopsy, or significant traumatic injury < 28 days prior to Day 1 therapy.
    2. Anticipation of need for major surgical procedures during the course of the study.
    3. Core biopsy within 7 days prior to Day 1 therapy.
  11. Patients must not be pregnant/breastfeeding and must agree to practice adequate contraception.  Breastfeeding should be discontinued if the mother is treated with aflibercept (VEGF Trap).  Patients must not be pregnant because animal studies show that compounds with a similar mechanism of action are teratogenic; data on the teratogenicity of aflibercept (VEGF Trap) is not yet available.
  12. Patients with clinically significant cardiovascular disease:
    1. History of ischemic or hemorrhagic stroke within past 6 months
    2. Uncontrolled hypertension, defined as blood pressure >140/90 mmHg or systolic BP >180 mmHg if diastolic blood pressure <90 mmHg, on at least 2 repeated determinations on separate days within past 3 months
    3. Myocardial infarction, CABG or unstable angina within past 6 months
    4. New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months
    5. Clinically significant peripheral vascular disease within past 6 months
    6. Pulmonary embolism, DVT, or other thromboembolic event within past 6 months.
  13. Evidence of bleeding diathesis or coagulopathy or INR >1.5.
  14. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with aflibercept (VEGF Trap).  Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  15. Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
  16. Patients must not have received prior therapy with aflibercept (VEGF Trap) for any indication.
  17. Inclusion of Women and Minorities:  Both men and women and members of all races and ethnic groups are eligible for this trial.
  18. Patients will not be excluded based on anticonvulsant use.
  19. Patients on full-dose anticoagulants (e.g. warfarin, low molecular-weight heparin) are not eligible.  Prophylactic doses are permitted.

Eligibility Criteria For Arm 1 (Aflibercept [VEGF Trap] + RT +TMZ) Patients Only
 

  1. Diagnosis will have been established by biopsy or resection 14-28 days prior to registration.  In order to permit healing, patients should not receive Day 1 of treatment with VEGF-Trap until at least 28 days after surgery.
  2. Patients must not have had prior cranial RT.
  3. Patients must have a plan to begin partial brain RT on the same day as the first dose of TMZ.  The first aflibercept (VEGF Trap) infusion will be scheduled for 2 weeks after the start of RT and TMZ.  Please refer to Section 6.3.2 of the protocol for detailed RT guidelines and exclusions.
  4. Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.