Please select the eligibility criteria that correspond to the clinical trial below.
Title: Adenovirus-Mediated Delivery of Herpes Simplex Virus Thymidine Kinase Administration Improves Outcome of Recurrent High-Grade Glioma
Brief Summary: Malignant gliomas are the most common primary brain tumor in adults, but the prognosis for patients with these tumors remains poor despite advances in diagnosis and standard therapies such as surgery, radiation therapy, and chemotherapy. The advantages of ADV-TK gene therapy highlight its efficacy and safety for glioma patients. This clinical trial was conducted to assess the anti-tumor efficacy and safety of intraarterial cerebral infusion of replication-deficient adenovirus mutant ADV-TK, in combination with systemic intravenous GCV administration in patients with recurrent high-grade glioma.


Options:
A: 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
B: 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
C: 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
D: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed glioblastoma
* Measurable disease by MRI
* Completed standard first-line treatment for glioblastoma including surgery (unless not received due to anatomical location), radiotherapy and temozolomide (last dose given at least 28 days prior to enrollment)

  * No other prior treatment for glioblastoma except Gliadel or steroids
* Recurrent or progressive disease after standard first-line treatment

  * No disease progression within 3 months of completion of radiotherapy
* No intra- or peri-tumoral hemorrhage

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* Mini-mental status score ≥ 15
* Life expectancy ≥ 12 weeks
* Serum bilirubin, ALT/AST, creatinine, and urine protein normal
* Adequate bone marrow reserve
* Not pregnant or nursing
* Normal ECG
* No history of familial long QT syndrome
* No absorption or swallowing difficulties
* No uncontrolled hypertension or cardiac ventricular arrhythmias
* No current or history of uncontrolled hypertension or requiring maximal doses of calcium channel blockers
* No severe or uncontrolled disease
* No history of lung disease
* No recent hemorrhage or hemoptysis
* No known hypersensitivity to cediranib maleate, gefitinib, or any excipients
* No history of other malignancies except adequately treated basal cell or squamous cell carcinoma or carcinoma in situ within the past 5 years, unless disease-free for 2 years with tissue diagnosis
* No known HIV positivity
* No known hepatitis B or C infection
* No unhealed surgical incision
* Not involved in planning or conducting this study

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Recovered from prior anticancer therapy, including radiotherapy
* At least 3 months since prior cranial radiation
* At least 30 days since prior investigational drugs
* At least 28 days since prior craniotomy
* At least 2 weeks since prior enzyme-inducing antiepileptic drugs
* At least 2 weeks since prior and no concurrent dexamethasone (\> 8 mg/day) or equivalent
* At least 14 days since prior major surgery or brain biopsy
* No concurrent steroids OR on stable dose 5 days prior to baseline MRI
* No other concurrent anticancer therapy, except for steroids (dexamethasone only)
* No previous enrollment on the current study
* No prior inhibitors of angiogenesis, EGFR, or downstream targets
* No prior radiosurgery or brachytherapy

Answer: C