Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma
Brief Summary: The purpose of this research study is to find out whether adding an experimental vaccine called rindopepimut (also known as CDX-110) to the commonly used drug bevacizumab can improve progression free survival (slowing the growth of tumors) of patients with relapsed EGFRvIII positive glioblastoma.


Options:
A: Inclusion Criteria:

* unifocal, supratentorial recurrent glioma
* contrast enhancement on T1-weighted MRI and/or Amino-Acid-PET-positive high-grade tumor areas
* indication re-irradiation
* age ≥ 18 years of age
* Karnofsky Performance Score ≥60
* For women with childbearing potential, (and men) adequate contraception.
* Ability of subject to understand character and individual consequences of the clinical trial
* Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

* Multifocal Glioma or Gliomatosis cerebri
* refusal of the patients to take part in the study
* previous re-irradiation or prior radiosurgery or prio treatment with interstitial radioactive seeds
* time interval of \< 6 months after primary radiotherapy
* Patients who have not yet recovered from acute toxicities of prior therapies
* Known carcinoma \< 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
* Pregnant or lactating women
* Participation in another clinical study or observation period of competing trials, respectively.
B: Inclusion Criteria:

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

1. Age ≥18 years of age.
2. Histologic diagnosis of glioblastoma (WHO Grade IV).
3. Documented EGFRvlll positive tumor status (central lab confirmation).
4. First or second relapse of de novo glioblastoma or first diagnosis or first relapse of secondary glioblastoma.
5. Previous treatment must include surgery, conventional radiation therapy and temozolomide (TMZ).
6. Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy.
7. KPS of ≥ 70%.
8. If applicable, systemic corticosteroid therapy must be at a dose of ≤ 4 mg of dexamethasone or equivalent per day during the week prior to Day 1.
9. Evaluable disease in Groups 1 and 2; measurable disease in Group 2C
10. Life expectancy \> 12 weeks.
11. Patients in Group 2 and 2C must have had disease progression while receiving bevacizumab or within 2 months of treatment with bevacizumab.

Exclusion Criteria:

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

1. Subjects unable to undergo an MRI with contrast.
2. History, presence, or suspicion of metastatic disease
3. Prior receipt of vaccination against EGFRvIII.
4. Any known contraindications to receipt of study drugs, including 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.
5. Use of non-protein based investigational therapy within 14 days prior to Day 1 or use of antibody-based investigational therapy within 28 days prior to Day 1.
6. Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
7. Evidence of recent hemorrhage on screening MRI of the brain
8. Evidence of current drug or alcohol abuse.
9. Patients in Group 1 must not have received prior treatment with bevacizumab.
C: Inclusion Criteria at Enrollment (before PD1):

* Newly diagnosed, histologically confirmed glioblastoma not previously treated with chemotherapy or radiotherapy
* If female and not postmenopausal (less than \[\<\] 12 months of amenorrhea) or surgically sterile, must agree to use a highly effective contraceptive method during the treatment period and for at least 6 months after the last dose of study drug
* Karnofsky performance status (KPS) greater than or equal to (\>/=) 60
* Mandatory tissue collection during pre-study surgery or biopsy for confirmation of the diagnosis and pathology
* Craniotomy or intracranial biopsy site must be adequately healed. Study treatment should be initiated \> 28 days following the last surgical procedure

Inclusion Criteria at Randomization (following PD1):

* Documented PD1 according to RANO criteria
* Eligibility for second-line treatment with lomustine and bevacizumab as investigational medicinal products
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Bevacizumab well tolerated and not interrupted for longer than 60 days during first-line treatment
* Tissue submission among participants for whom operation/re-operation is indicated before second-line treatment starts; operation/re-operation performed \>/=28 days after last bevacizumab administration and second-line treatment initiated \>/=28 days after surgical wound healed
* Randomization within 28 days after PD1 among participants for whom operation/re-operation is not necessary
* First administration of second-line treatment no later than 2 days from randomization

Exclusion Criteria at Enrollment (before PD1):

* Any prior chemotherapy for glioblastoma and low-grade astrocytomas
* Any prior radiotherapy to the brain or prior radiotherapy resulting in a potential overlap in the radiation field
* Prior or current anti-angiogenic treatment
* Treatment with any other investigational drug within 28 days or 2 investigational agent half-lives (whichever is longer) prior to first study treatment
* Inadequate hematological, renal, or liver function
* Inadequately controlled hypertension
* Prior history of gastrointestinal perforation or abscess
* Clinically significant cardiovascular disease
* History or evidence of central nervous system disease unrelated to cancer unless adequately treated with standard medical therapy
* History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
* Serious non-healing wound, active ulcer, or untreated bone fracture
* Known hypersensitivity to any component of bevacizumab/placebo or any of the study drugs
* Active infection requiring IV antibiotics at start of study treatment
* Other malignancy within 5 years prior to study enrollment, except for carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ treated with curative intent
* Pregnant or lactating women
* Participation in any other study
D: Inclusion Criteria:

* Adult patients, \>/=18 years of age
* Diagnosis of recurrent glioblastoma multiforme (Grade IV)
* Previous treatment with temozolomide and radiotherapy
* First recurrence after standard adjuvant treatment (surgery, followed by radiotherapy and chemotherapy)
* Adequate hematological, biochemical and organ functions

Exclusion Criteria:

* Previous treatment with Avastin or other anti-angiogenic drugs
* Residual relevant toxicity resulting from previous therapy
* Radiotherapy within the 3 months prior to the diagnosis of disease progression
* Chemotherapy in the previous 4 weeks
* Other active or inactive malignancies (except for carcinoma in situ of the cervix, of the prostate or basal cell carcinoma)
* Clinically significant cardiovascular diseases

Answer: B