Please select the eligibility criteria that correspond to the clinical trial below.
Title: An International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF With Adjuvant Temozolomide in Patients With Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma
Brief Summary: This 2-arm, randomized, phase III study will investigate the efficacy and safety of the addition of rindopepimut (an experimental cancer vaccine that may act to promote anti-cancer effects in patients who have tumors that express the EGFRvIII protein) to the current standard of care (temozolomide) in patients with recently diagnosed glioblastoma, a type of brain cancer.

All patients will be administered temozolomide, the standard treatment for glioblastoma. Half the patients will be randomly assigned to receive rindopepimut and half the patients will be randomly assigned to receive a control called keyhole limpet hemocyanin.

Patients will be treated in a blinded fashion (neither the patient or the doctor will know which arm of the study the patient is on). Patients will be treated until disease progression or intolerance to therapy and all patients will be followed for survival.


Options:
A: Inclusion criteria: Diagnosis: newly diagnosed glioblastoma in elderly patients

1. Signed informed consent
2. Age \> 65 years
3. Newly diagnosed supratentorial glioblastoma
4. Eligible for first infusion of bevacizumab \> 28 and \> 49 days after surgery for glioblastoma
5. Karnofsky performance score 60 or more
6. Paraffin-embedded tissue for central pathology review
7. Stable or decreasing corticosteroid dose within 5 days prior to enrolment
8. Adequate haematological function:
9. Adequate liver function
10. Adequate renal function

Exclusion criteria:

1. Karnofsky performance score 50 or less
2. Evidence of recent hemorrhage on postoperative brain MRI
3. Tumor with infiltration of retina, optic nerve, optic chiasm or brainstem
4. Any prior chemotherapy including carmustine-containing wafers (Gliadel®) or immunotherapy for glioblastoma or lower grade astrocytomas
5. Any prior radiotherapy to the brain or prior radiotherapy resulting in a potential overlap in the radiation field
6. Inadequately controlled hypertension
7. History of hypertensive crisis or hypertensive encephalopathy
8. New York Heart Association (NYHA) grade II or higher congestive heart failure
9. Myocardial infarction or unstable angina within 6 months prior to enrolment
10. Stroke or transitory ischemic attack within 6 months prior to enrolment
11. Other significant vascular disease within 6 months prior to enrolment
12. History of = grade 2 haemoptysis within 1 month prior to enrolment
13. Bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation
14. Major surgical procedure, open biopsy, intracranial biopsy, ventriculoperitoneal shunt or significant traumatic injury within 28 days prior to first dose of bevacizumab
15. Core biopsy (excluding intracranial biopsy) or other minor surgical procedure within 7 days prior to first dose of bevacizumab
16. Abdominal fistula or gastrointestinal perforation within 6 months prior to enrolment
17. Intracranial abscess within 6 months prior to enrolment
18. Serious non-healing wound, active ulcer or untreated bone fracture
19. Pregnancy or lactation
20. Fertile women \< 2 years after last menstruation and men unwilling or unable to use effective means of contraception
21. Active malignancy that may interfere with the study treatment at the investigator?s and PI discretion
B: 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
C: Inclusion Criteria-

Among other criteria, patients must meet the following conditions to be eligible for the study:

1. Adult patients, ≥ 18 years old
2. Newly diagnosed glioblastoma
3. Attempted surgical resection followed by conventional chemoradiation
4. Documented EGFRvIII positive tumor status by a Sponsor designated laboratory
5. No evidence of progressive disease from the post-operative period to the post-chemoradiation period
6. Candidate for, and agrees to receive, adjuvant (maintenance) temozolomide therapy
7. Systemic corticosteroid therapy at ≤2 mg of dexamethasone or equivalent per day for at least 3 days prior to randomization
8. WHO-ECOG Performance Status ≤ 2
9. Patients of childbearing/reproductive potential will be instructed to use birth control as defined by your doctor.

Exclusion Criteria-

Among other criteria, patients who meet the following conditions are NOT eligible for the study:

1. Stereotactic biopsy only (without further surgical resection)
2. Presence of diffuse leptomeningeal disease, gliomatosis cerebri, or infratentorial disease.
3. History, presence, or suspicion of metastatic disease
4. Patients who have received any additional treatment for glioblastoma, aside from surgical resection and chemoradiation with temozolomide
5. Active systemic infection requiring treatment
6. History of any malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer, cured, early-stage prostate cancer in a patient with PSA level less than ULN,or other carcinoma in situ that has been adequately treated and cured.
7. Planned major surgery
8. Evidence of current drug or alcohol abuse
9. Known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins
10. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with participating in a clinical trial
11. Women who are pregnant or lactating
D: Inclusion Criteria:

* adult patients, 18-70 years of age;
* glioblastoma, confirmed histologically;
* no previous chemotherapy or radiotherapy for glioblastoma;
* non-methylated MGMT promoter in the tumor.

Exclusion Criteria:

* prior systemic treatment for glioblastoma multiforme;
* prior treatment with Avastin;
* significant cardiovascular disease;
* other active malignant disease.

Answer: C