Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Non Comparative Phase II Trial With Bevacizumab and Fotemustine in the Treatment of Recurrent Glioblastoma
Brief Summary: This randomized, non-comparative study will evaluate the efficacy and safety of Avastin (bevacizumab) in patients with recurrent glioblastoma. Patients will be randomized to receive Avastin 10 mg/kg intravenously every 2 weeks or fotemustine 75 mg/m2 on days 1, 8 and 15, followed by, after a 5 weeks interval, 100 mg/m2 intravenously every 3 weeks. Treatment with fotemustine serves as a calibration arm and no formal efficacy comparison will be made between the two treatment arms. The anticipated time of study treatment is until disease progression or unacceptable toxicity.


Options:
A: Inclusion Criteria:

* Histologically confirmed WHO grades 3 to 4 malignant glioma
* Diagnosed recurrence or progression by clinical or radiological evidence
* Fit for intraarterial infusion and intravenous chemotherapy
* Adequate hepatic, renal, and hematologic function.
* Legal age ≥18 years
* Life expectancy ≥12 weeks
* Eastern Cooperative Oncology Group performance (ECOG) ≥2
* Chemotherapy completion ≥4 weeks prior and recovery from drug induced toxicities.

Exclusion Criteria:

* Active pregnancy
* Prior gene therapy
* Second primary tumor
* Gravidity, lactation, hypersensitivity to antiviral drugs, immunologic deficit, active uncontrolled infections
* Requiring treatment with warfarin or any other anticoagulants
B: 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.
C: 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
D: Inclusion Criteria:

* Unifocal, supratentorial recurrent glioblastoma
* Prior course of standard treatment
* Complete resection of all contrast enhancing areas
* age ≥ 18 years of age
* Karnofsky Performance Score 60% or higher
* 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 glioblastoma of gliomatosis cerebri
* Time interval of less than 6 months after primary radiotherapy
* Previous re-irradiation or prior radiosurgery of prior treatment with interstitial radioactive seeds
* refusal of the patients to take part in the study
* 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.

Answer: C