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: Key Inclusion Criteria:

* newly diagnosed glioblastoma
* World Health Organization (WHO) performance status less than or equal to (\<=2)
* stable or decreasing corticosteroid dose within 5 days prior to randomization

Key Exclusion Criteria:

* evidence of recent hemorrhage on postoperative magnetic resonance imaging (MRI) of brain
* any prior chemotherapy or immunotherapy for glioblastomas and low grade astrocytomas
* any prior radiotherapy to brain
* clinically significant cardiovascular disease
* history of greater than or equal to (\>=) grade 2 hemoptysis within 1 month prior to randomization
* previous centralized screening for Methylguanine-DNA methyltransferase (MGMT) status for enrollment into a clinical trial
B: Inclusion Criteria:

* Must have a clinical diagnosis of glioblastoma (GBM).
* Must have a confirmed epidermal growth factor receptor amplification in tumor tissue.
* Must have a Karnofsky Performance Status (KPS) \>= 70 at assessment \<= 14 days prior to randomization (N/A to the sub-study).
* Must have recovered from effects of surgery, postoperative infection and other complications of surgery.
* Must have adequate bone marrow, renal, and hepatic function (For the sub-study, the participant must have adequate bone marrow and renal function and have mild-to-moderate hepatic impairment).

Exclusion Criteria:

* Multifocal, recurrent or metastatic GBM or gliomatosis cerebri (For the sub-study, the participant can have multifocal GBM and glimatosis cerebri but can't have recurrent or metastatic GBM).
* Prior chemo therapy or radiosensitizer for head and neck cancer.
* Prior radiotherapy to the head or neck in overlap of radiation fields.
* Prior therapy for glioblastoma or other invasive malignancy.
* Prior, concomitant or planned treatment with Novo Tumor Treatment Fields (Novo-TTF), EGFR-targeted therapy, bevacizumab, Gliadel wafers or other intratumoral or intracavity anti-neoplastic therapy.
C: Inclusion Criteria:

Adult participants (greater than or equal to 18 years old):

* Histologically confirmed de novo (primary) glioblastoma with unequivocal tumor progression or recurrence.
* In case of testing at the time of first progression: either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy
* Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registration in the trial.
* Availability of adequate biological material (formalin-fixed paraffin embedded \[FFPE\] tumor) for central testing of Epithelial Growth Factor Receptor (EGFR) amplification
* Presence of EGFR amplification confirmed by central assessment; participants with undetermined EGFR status are excluded
* World Health Organization (WHO) Performance status 0 - 2
* No more than one line of chemotherapy (concurrent and adjuvant Temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization.
* Post surgery MRI within 48 hours following surgery, however an MRI scan has to be done within 2 weeks prior to randomization.
* Surgery completed at least 2 weeks before randomization and patients should have fully recovered as assessed by investigators.
* Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula.
* Liver function: bilirubin \< 1.5× upper limit of the normal range (ULN), alkaline phosphatase and transaminases (ASAT) \< 2.5× ULN

Pediatric sub-study participants (less than 18 years old):

* Histologically proven high grade glioma (HGG: WHO grade III glioma \[e.g anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma\], grade IV glioma \[e.g. glioblastoma, gliosarcoma\] or diffuse intrinsic pontine glioma \[DIPG\]).
* Must either have recurrent/progressive tumor or, if newly diagnosed, have completed any planned radiation therapy at least 4 weeks prior to first dose of ABT-414.
* The tumor tissue must have been determined to have EGFR amplification, (by local or other testing service).
* Availability of adequate biological material for retrospective confirmatory central testing of EGFR amplification
* Participant has sufficiently recovered from previous therapy. The investigator believes that benefit of treating the pediatric subject with ABT-414 outweighs the expected risks and that this treatment is in the best interests of the pediatric subject.
* Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula for pediatric patients ≥12 years of age and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m\^2 by modified Schwartz equation for pediatric patients \< 12 years of age.
* Liver function: Total bilirubin ≤ 1.5× upper limit of the normal range (ULN), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) \<= 3× ULN. Participants with Gilbert's syndrome documented in medical history may be enrolled if total bilirubin is \< 3 times ULN. Not allowed are participants with known chronic liver disease and/or cirrhosis.

Exclusion Criteria:

Adult population (greater than or equal to 18 years old):

* Prior treatment with nitrosoureas
* Prior treatment with bevacizumab
* Previous exposure to Epithelial Growth Factor Receptor (EGFR) targeted agents, including EGFRvIII targeting agents
* Prior discontinuation of temozolomide chemotherapy for toxicity reasons
* Prior Radiation Therapy (RT) with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
* Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomization, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
* No history of wheat allergies and Coeliac disease.
* No EIAED, patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). Patients previously on EIAED must be fully switched to non-EIAED at least 2 weeks prior to randomization.

Pediatric sub-study (less than 18 years old):

* (For recurrent disease) No prior RT with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
* No current or recent (within 4 weeks or 5 half-lives \[whichever is shorter\] before enrollment) treatment with another investigational drug
* Female participants of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
D: 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

Answer: D