Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase III Double-blind Placebo-Controlled Trial of Conventional Concurrent Chemoradiation and Adjuvant Temozolomide Plus Bevacizumab Versus Conventional Concurrent Chemoradiation and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma
Brief Summary: This randomized phase III trial studies temozolomide (TMZ) and radiation therapy (RT) to compare how well they work with or without bevacizumab in treating patients with newly diagnosed glioblastoma or gliosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may find tumor cells and help kill them. It is not yet known whether temozolomide and radiation therapy are more effective when given together with or without bevacizumab in treating glioblastoma or gliosarcoma.


Options:
A: Inclusion Criteria:

* Histologically confirmed supratentorial anaplastic astrocytoma or glioblastoma
* Age \> 65
* Karnofsky performance score \> 60%
* Neutrophilic granulocyte count \> 1500/µl
* Platelet count \> 100 000/µl
* Hemoglobin \> 10 g/dl
* Serum creatinine \< 1.5 times the lab's upper normal limit
* AST or ALT \< 3 times the lab's upper normal limit
* Alkaline phosphatase \< 3 times the lab's upper normal limit
* No previous systemic chemotherapy
* No previous radiotherapy to the brain
* Written consent

Exclusion Criteria:

* Serious medical or neurological condition with a poor prognosis
* HIV infection
* Second cancer requiring radiotherapy or chemotherapy (contact the study coordinat if necessary)
* Hypersensitivity to temozolomide
* Conditions associated with regular vomiting that might affect oral administration of the drugs
* Psychological, familial, social or geographical circumstances with major implications for compliance with the study visit schedule
* Patient was taking part in other intervention studies within a month of starting this study
B: DISEASE CHARACTERISTICS: Histologically confirmed newly diagnosed glioblastoma multiforme by biopsy or surgical resection Grade IV disease Initial diagnosis no greater than 6 weeks prior to study

PATIENT CHARACTERISTICS: Age: 18 to 70 Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST or ALT less than 2.5 times ULN Alkaline phosphatase less than 2.5 times ULN No chronic hepatitis B or C Renal: Creatinine no greater than 1.5 times ULN Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known HIV infection No medical condition that would interfere with oral medication intake (e.g., frequent vomiting or partial bowel obstruction) No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer No serious medical, psychological, familial, sociological, or geographical condition that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa No concurrent biologic therapy No concurrent immunotherapy Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: At least 14 days of prior corticosteroids at a stable dose required Concurrent corticosteroids allowed Radiotherapy: No prior radiotherapy No concurrent stereotactic boost radiotherapy Surgery: See Disease Characteristics No concurrent surgery for tumor debulking Other: No other concurrent investigational drugs
C: Inclusion Criteria:

1. Pathological evidence of GBM using WHO classification criteria.
2. \> 18 years of age.
3. Received maximal debulking surgery and radiotherapy concomitant with Temozolomide (45-70Gy):

   1. Patients may enroll in the study if received Gliadel wafers before entering the trial
   2. Any additional treatments received prior to enrollment will be considered an exclusion.
   3. Minimal dose for concomitant radiotherapy is 45 Gy
4. Karnofsky scale ≥ 70
5. Life expectancy at least 3 months
6. Participants of childbearing age must use effective contraception.
7. All patients must sign written informed consent.
8. Treatment start date at least 4 weeks out from surgery.
9. Treatment start date at least 4 weeks out but not more than 7 weeks from the later of last dose of concomitant Temozolomide or radiotherapy.

Exclusion Criteria:

1. Progressive disease (according to MacDonald Criteria). If pseudoprogression is suspected, additional imaging studies must be performed to rule out true progression.
2. Actively participating in another clinical treatment trial
3. Pregnant
4. Significant co-morbidities at baseline which would prevent maintenance Temozolomide treatment:

   1. Thrombocytopenia (platelet count \< 100 x 103/μL)
   2. Neutropenia (absolute neutrophil count \< 1.5 x 103/μL)
   3. CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
   4. Significant liver function impairment - AST or ALT \> 3 times the upper limit of normal
   5. Total bilirubin \> upper limit of normal
   6. Significant renal impairment (serum creatinine \> 1.7 mg/dL)
5. Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
6. Infra-tentorial tumor
7. Evidence of increased intracranial pressure (midline shift \> 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
8. History of hypersensitivity reaction to Temozolomide or a history of hypersensitivity to DTIC.
D: Inclusion Criteria:

* Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization \[WHO\] grade IV) confirmed by central review prior to step 2 registration
* Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of O-6-methylguanine-DNA methyltransferase (MGMT) and determination of molecular profile

  * Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; at least 1 cubic centimeter of tissue composed primarily of tumor must be present
  * CUSA (Cavitron ultrasonic aspirator)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged
  * Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis
  * The tumor tissue should be sent as soon as possible to maximize the likelihood of eligibility; tumor tissue should be submitted by 4 weeks after the surgical procedure so that the study registration and treatment can commence by the mandatory 5 week post-surgery outer limit
  * Sites must submit tissue fir central review in order to obtain the MGMT analysis; patients from sites not following protocol-specified process for obtaining MGMT results will be made ineligible
* The tumor must have a supratentorial component
* History/physical examination within 14 days prior to step 2 registration
* The patient must have recovered from the effects of surgery, postoperative infection, and other complications before step 2 registration
* A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy; the postoperative scan must be performed within 28 days prior to step 1 registration

  * An MRI or computed tomography (CT) scan (potentially in addition to the postoperative scan) must be obtained within 10 days prior to the start of radiation therapy and must not demonstrate significant postoperative hemorrhage defined as \> 1 cm diameter of blood; if \> 1 cm of acute blood is detected, the patient will be ineligible for this trial; the radiation planning MRI or CT scan may be used to determine presence of hemorrhage
  * Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided pre- and postoperative contrast-enhanced CT scans are obtained and are of sufficient quality; preoperative and postoperative scans must be the same type; such patients cannot be enrolled into the advanced imaging component
* Documentation of steroid doses within 14 days prior to step 2 registration
* Karnofsky performance status \>= 70
* Absolute neutrophil count (ANC) \>= 1,800 cells/mm\^3
* Platelets \>= 100,000 cells/mm\^3
* Hemoglobin \>= 10.0 g/dL (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 10.0 g/dl is acceptable)
* Blood urea nitrogen (BUN) =\< 30 mg/dL within 14 days prior to step 2 registration
* Creatinine =\< 1.7 mg/dl within 14 days prior to step 2 registration
* Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio \> 0.5, 24-hour urine protein should be obtained and the level should be \< 1000 mg
* Bilirubin =\< 2.0 mg/dl within 14 days prior to step 2 registration
* Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 3 x normal range within 14 days prior to step 2 registration
* Systolic blood pressure =\< 160 mg Hg or diastolic pressure =\< 90 mm Hg within 14 days prior to step 2 registration
* Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior to step 2 registration
* Prothrombin time/international normalized ratio (PT INR) \< 1.4 for patients not on warfarin confirmed by testing within 14 days prior to step 2 registration
* Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight \[LMW\] heparin) must meet both of the following criteria:

  * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  * In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of LMW heparin
* Patient must provide study specific informed consent prior to study entry
* Women of childbearing potential and male participants must practice adequate contraception
* For females of child-bearing potential, negative serum pregnancy test within 14 days prior to step 2 registration

Exclusion Criteria:

* Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for \>= 3 years; (for example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
* Recurrent or multifocal malignant gliomas
* Metastases detected below the tentorium or beyond the cranial vault
* Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or bevacizumab; prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
* Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
* Severe, active co-morbidity, defined as follows:

  * Unstable angina and/or congestive heart failure within the last 6 months
  * Transmural myocardial infarction within the last 6 months
  * Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of \>= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of step 2 registration
  * New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
  * History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
  * Serious and inadequately controlled cardiac arrhythmia
  * Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
  * Evidence of bleeding diathesis or coagulopathy
  * Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for tumor resection
  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
  * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
  * Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive
  * Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
  * Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
* Pregnant or lactating women
* Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study
* For American College of Radiology Imaging Network (ACRIN) 6686 Advanced Imaging: inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker)

Answer: D