Please select the eligibility criteria that correspond to the clinical trial below.
Title: Amino-acid PET Versus MRI Guided Re-irradiation in Patients With Recurrent Glioblastoma Multiforme - a Randomised Phase II Trial
Brief Summary: This study is designed to evaluate the impact of radiotherapy target volume delineation based on AA-PET compared to target volume delineation based on contrast enhanced T1 weighted MRI (T1Gd-MRI) on the clinical outcome of patients with recurrent glioblastoma (GBM) as well as concerning therapeutic safety of the respective strategy.


Options:
A: Inclusion Criteria:

* Local recurrence of GBM (WHO grade IV) and either not eligible for tumor resection or with macroscopic residual tumor after resection of recurrent GBM
* Recurrent tumor visible on AA-PET and MRI-T1-Gd with the diameter measuring 1 cm to 6 cm by either technique
* Target volume definition possible according to both study arms
* Previous radiation therapy of the primary with a maximal total dose 60 Gy
* At least 9 months since the end of pre-irradiation and randomisation
* At most 2 prior chemotherapy regimes
* Start of radiation therapy possible within 2 weeks from AA-PET
* Karnofsky Performance Score (KPS) ≥ 70%
* Age ≥ 18 years
* Written informed consent (IC) obtained

Exclusion Criteria:

* - No histological confirmation of Glioma at initial diagnosis)
* Recent (≤ 4 weeks before IC) histological result showing no tumor recurrence
* No recurrent tumor detectable on last AA-PET or MRI-T1-Gd
* Technical impossibility to use existing AA-PET for RT-planning
* No prior radiation treatment to the primary tumor
* less than 9 months between the end of first radiation treatment and randomisation
* more than 2 previous chemotherapy regimes or previous treatment with Avastin or other molecular targeted therapies
* less than 2 weeks between application of chemotherapy and randomisation
* additional chemotherapy or molecular targeted therapy or further surgery planned before diagnosis of further tumor progression after study intervention
* pregnancy, nursing or patient not willing to prevent pregnancy during treatment
B: Inclusion Criteria:

* Signed Informed Consent Form
* Age ≥ 18 years
* Histologically confirmed GBM in first or second relapse
* Radiographic demonstration of disease progression following prior therapy
* Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on MRI performed within 14 days prior to first treatment (Day 0)
* An interval of ≥ 4 weeks since prior surgical resection
* Prior standard radiation for GBM
* Prior chemotherapy: first-relapse subjects
* Prior chemotherapy: second-relapse subjects
* Recovery from the effects of prior therapy, including the following: 4 weeks from cytotoxic agents (except 6 weeks from nitrosoureas, 3 weeks from procarbazine, 2 weeks from vincristine); 4 weeks from any investigational agent; 1 week from non-cytotoxic agents; 8 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field
* Prior therapy with gamma knife or other focal high-dose radiation is allowed but the subject must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field
* Karnofsky performance status ≥ 70
* Life expectancy \> 12 weeks
* Use of an effective means of contraception in males and in females of childbearing potential
* Ability to comply with study and follow-up procedures

Exclusion Criteria:

* Prior treatment with irinotecan, bevacizumab, or another VEGF or VEGFR-targeted agent
* Prior treatment with prolifeprospan 20 with carmustine wafer
* Prior intracerebral agents
* Need for urgent palliative intervention for primary disease (e.g., impending herniation)
* Evidence of recent hemorrhage on baseline MRI of the brain with the following exceptions: Presence of hemosiderin; Resolving hemorrhagic changes related to surgery; Presence of punctate hemorrhage in the tumor
* Received more than two treatment regimens for Grade III and/or Grade IV glioma
* Blood pressure of \> 150 mmHg systolic and \> 100 mmHg diastolic
* History of hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater CHF
* History of myocardial infarction or unstable angina within 6 months prior to Day 0
* History of stroke or transient ischemic attack within 6 months prior to study enrollment
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 0
* Evidence of bleeding diathesis or coagulopathy
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
* History of intracerebral abscess within 6 months prior to Day 0
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
* Minor surgical procedures (excluding placement of a vascular access device), stereotactic biopsy, fine needle aspirations, or core biopsies within 7 days prior to Day 0
* Serious non-healing wound, ulcer, or bone fracture
* Pregnancy (positive pregnancy test) or lactation
* Known hypersensitivity to any component of bevacizumab
* History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix)
* Pregnant or nursing females
* Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmia requiring medication
* Subjects unable to undergo an MRI with contrast
C: Inclusion Criteria:

* Patients 18 years or older with KPS \> 60, with life expectancy of \> 8 weeks with radiographically proven recurrent, intracranial Glioblastoma multiforme or Gliosarcoma; patients must have documentation of Rb positive disease.
* All patients must sign an informed consent and must have signed an authorization for the release of their protected health information.
* Patients must have had prior external beam radiation and temozolomide chemotherapy; there is no limit to the number of prior chemotherapies used; patients may be treated in their first, second or third relapse
* Patients must have recovered from the toxic effects of prior therapy
* Patients must have adequate bone marrow function and renal function before starting therapy. A pre-study EKG with a normal QT interval is required for all patients
* Patients must have shown unequivocal evidence for tumor progression by MRI scan and on a steroid dose that has been stable for at least 7 days.
* Patients must have an interval of greater than or equal to 42 days from the completion of radiation therapy to study entry.
* A subset of 15 patients will be enrolled prior to a planned, indicated surgical resection. Patients can be enrolled pre-operatively only if they are surgical candidates, do not have evidence of an acute intracranial hemorrhage and are able to start protocol treatment in a window of 7 days before surgery.
* Male and female patients with reproductive potential must use an approved contraceptive method. Women of childbearing potential must have a negative beta-HCG pregnancy test
* Blocks or slides of tumor tissue from a previous surgery must be available to do IHC Rb staining. Patients with negative tumors (Rb negative) will be excluded from the study.

Exclusion Criteria:

* Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
* Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
* Patients on enzyme-inducing anti-epileptic drugs or other drugs that cause CYP3A enzyme induction or inhibition will not be eligible
D: Inclusion Criteria:

* Confirmation of recurrent glioblastoma
* Life expectancy ≥ 12 weeks
* Received only one prior systemic chemotherapy regimen and this regimen must contain temozolomide

Exclusion Criteria:

* Patients on enzyme-inducing anti-epileptic drugs within 3 weeks prior to randomisation
* Poorly controlled hypertension
* Previous anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) therapy

Answer: A