Please select the eligibility criteria that correspond to the clinical trial below.
Title: Adjuvant Stereotactic Fractionated Radiotherapy to the Resection Cavity in Recurrent Glioblastoma
Brief Summary: This multi-center randomized controlled phase II trial will investigate the impact of stereotactic fractionated radiotherapy to the resection cavity of complete resected recurrent glioblastoma on progression free survival. As secondary endpoints, overall survival, safety and toxicity as well as early response criteria on MRI, quality of life and neurocognitive function will be assessed. Chemotherapy will not be part of the protocol, however, additional treatment will be possible upon investigators best choice.


Options:
A: 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.
B: 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
C: Inclusion Criteria:

1. A previous diagnosis of glioblastoma (histologically verified) and presenting with a first progression/recurrence documented by MRI.
2. Indication for treatment with chemotherapeutic alkylating agents (i.e. temozolomide OR lomustine including PCV treatment).
3. Age 18 years or older.
4. Karnofsky performance status of 60 - 100 .
5. Not receiving another experimental treatment for glioblastoma at the moment of inclusion or during active treatment within the assigned group (i.e. control or disulfiram group).
6. Able to take oral medications.
7. No known allergy to disulfiram or copper.
8. Absolute neutrophil count ≥ 1,500/mcL and platelets ≥ 100,000/mcL
9. Serum/plasma copper and serum ceruloplasmin within institutional limits.

   a. However increased levels are seen together with ongoing acute phase reaction as determined by elevated C-reactive protein (ceruloplasmin is elevated as part of the same process) it is possible to retest after normalization of C-reactive protein.
10. Willing to refrain from ingestion of alcoholic beverages while on the study is a criteria to be randomized. However, once randomized alcohol abstinence only affects the group treated with disulfiram, and in this group it includes the entire period and one month after last dosage of disulfiram.

Exclusion Criteria:

1. Earlier treatment for progression (e.g. "rescue therapy")
2. History of idiopathic seizure disorder, psychosis or schizophrenia.
3. History of uncontrolled hypertension (i.e. systolic BP \> 180 mmHg) and a diagnosis of congestive heart failure
4. Received radiotherapy within the 3 months before the diagnosis of progression .
5. Addiction to alcohol or drugs.
6. Pregnant and/or breastfeeding.
7. Women of childbearing potential who do not have negative pregnancy test not older than 14 days before enrollment.
8. History of active liver disease, including chronic active hepatitis, viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice of any etiology or toxic hepatitis or inadequate hepatic function, defined as baseline ASAT and ALAT \> 2.5 X upper institutional limit and/or bilirubin \> 2.0 X upper institutional limit.
9. History of Wilson's disease or family member with Wilson's disease (unless excluded as a carrier by genetic test).
10. History of hemochromatosis or family member with hemochromatosis (unless excluded as a carrier by genetic test).
11. Nickel hypersensitivity (disulfiram mobilize nickel causing a brief increase in nickel concentrations before excretion. The initial increase may lead to hepatitis and predisposed patients).
12. Need for metronidazole, warfarin and/or theophylline medication (the metabolism may be influenced by disulfiram).
13. Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives (phenytoin, phenobarbital, chlordiazepoxide, imipramine, diazepam, isoniazid, metronidazole, warfarin, amitriptyline within 14 days prior to the first dose of disulfiram. Of note, lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with disulfiram).
14. Unfit for participation for any other reason judged by the including physician.
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