Please select the eligibility criteria that correspond to the clinical trial below.
Title: Primary Chemotherapy With Temozolomide Versus Radiotherapy in Patients With Low Grade Gliomas After Stratification for Genetic 1p Loss: A Phase III Study
Brief Summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether radiation therapy is more effective than temozolomide in treating gliomas.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared to temozolomide in treating patients with gliomas.


Options:
A: Inclusion Criteria:

1. Patients with primary intracranial tumours such as low-grade glioma, meningioma, craniopharyngiomas, ependymomas and other benign tumours considered for radical focal radiotherapy.
2. Tumours measuring upto 7 cms on maximum dimension on the CT/MRI.
3. Age 3 to 25 years.
4. NPS of 0-3.
5. Informed consent from patients or parents as appropriate.
6. Long-term follow up expected

Exclusion Criteria:

1. Previous radiotherapy.
2. Planned adjuvant chemotherapy.
3. Expected median survival of less than two years.
4. Patient not cooperative for planning and execution of SCRT.
B: Inclusion Criteria:

1. Pathological evidence of GBM using WHO classification criteria.
2. \> 18 years of age.
3. Received maximal debulking surgery and radiotherapy concomitant with Temozolomide (45-70Gy):

   1. Patients may enroll in the study if received Gliadel wafers before entering the trial
   2. Any additional treatments received prior to enrollment will be considered an exclusion.
   3. Minimal dose for concomitant radiotherapy is 45 Gy
4. Karnofsky scale ≥ 70
5. Life expectancy at least 3 months
6. Participants of childbearing age must use effective contraception.
7. All patients must sign written informed consent.
8. Treatment start date at least 4 weeks out from surgery.
9. Treatment start date at least 4 weeks out but not more than 7 weeks from the later of last dose of concomitant Temozolomide or radiotherapy.

Exclusion Criteria:

1. Progressive disease (according to MacDonald Criteria). If pseudoprogression is suspected, additional imaging studies must be performed to rule out true progression.
2. Actively participating in another clinical treatment trial
3. Pregnant
4. Significant co-morbidities at baseline which would prevent maintenance Temozolomide treatment:

   1. Thrombocytopenia (platelet count \< 100 x 103/μL)
   2. Neutropenia (absolute neutrophil count \< 1.5 x 103/μL)
   3. CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
   4. Significant liver function impairment - AST or ALT \> 3 times the upper limit of normal
   5. Total bilirubin \> upper limit of normal
   6. Significant renal impairment (serum creatinine \> 1.7 mg/dL)
5. Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
6. Infra-tentorial tumor
7. Evidence of increased intracranial pressure (midline shift \> 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
8. History of hypersensitivity reaction to Temozolomide or a history of hypersensitivity to DTIC.
C: DISEASE CHARACTERISTICS:

* Histologically confirmed low-grade glioma, including any of the following types:

  * Astrocytoma (gemistocytic, fibrillary, or protoplasmatic)
  * Oligoastrocytoma
  * Oligodendroglioma
* WHO grade II disease
* Supratentorial tumor location only
* RTOG neurological function 0-3
* Not a candidate for surgical treatment alone
* Requires treatment, as determined by ≥ 1 of the following criteria:

  * Age ≥ 40 years
  * Radiologically-proven progressive lesion
  * New or worsening neurological symptoms other than seizures only (e.g., focal deficits, signs of increased intracranial pressure, or mental deficits)
  * Intractable seizures, defined by both of the following criteria:

    * Experiences persistent seizures that interfere with everyday life activities except driving a car
    * Failed 3 anti-epileptic drug regimens, including ≥ 1 combination regimen
* Tumor material (paraffin-embedded) or histopathologic slides available

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* WHO 0-2

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3

Hepatic

* No chronic hepatitis B or C infection
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST or ALT ≤ 2.5 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN

Renal

* Creatinine ≤ 1.5 times ULN

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception during and for 6 months after completion of study treatment
* No known HIV positivity
* No other serious medical condition
* No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer
* No psychological, familial, sociological, or geographical condition that would preclude study participation
* No medical condition that would preclude receiving oral medication (e.g., frequent vomiting or partial bowel obstruction)

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent growth factors for elevating absolute neutrophil counts for the purpose of temozolomide administration
* No concurrent epoetin alfa
* No concurrent immunotherapy or biologic therapy

Chemotherapy

* No prior chemotherapy
* No other concurrent chemotherapy, including adjuvant chemotherapy for patients randomized to undergo radiotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy to the brain
* No concurrent integrated boost with intensity-modulated radiotherapy

Surgery

* Recovered from prior surgery
* No concurrent surgical tumor debulking

Other

* No prior randomization to this study
* No other concurrent investigational drugs
* No concurrent regular use of agents known to be radiosensitizers or radioprotectors (e.g., cyclooxygenase-2 inhibitors, thalidomide, or amifostine) during study radiotherapy

  * Occasional use of nonsteroidal anti-inflammatory drugs for pain allowed
D: Inclusion Criteria:

* Patients must have presumed resectable or partially resectable malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined). Patients who have previously received CAN-2409 + prodrug on this study may receive an additional CAN-2409 + prodrug course at recurrence if eligibility criteria are still met.
* Tumor must be accessible for injection and must not be located in the brainstem, midbrain, contained within the ventricular system, or located in an infratentorial location.
* Upfront patients must be planning to undergo standard radiation therapy.
* Patients must be 18 years of age or older.
* Performance status must be KPS ≥70.
* Patients must have SGOT (AST) \< 3x upper limit of normal.
* Patients must have serum creatinine \< 2mg/dl and calculated creatinine clearance \>10ml/min.
* Patients must have platelets \> 100,000/mm3 and WBC \> 3000/mm3.
* Patients of reproductive age must agree to use a medically accepted form of birth control while on the study.
* Patients must give study specific informed consent prior to enrollment. For re-administration, patients must be re-consented.
* Patients must be able to tolerate MRI scan procedure

Exclusion Criteria:

* Active liver disease including cirrhosis or hepatitis
* Patients on immunosuppressive drugs (with exception of corticosteroid)
* Known HIV+ patients.
* Patients with acute infections (viral, bacterial or fungal infections requiring therapy).
* Pregnant or breast feeding patients. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy.
* Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).
* Other serious co-morbid illness or compromised organ function.
* Patients may not receive chemotherapy until valacyclovir is completed and may not receive other investigational anti-tumor agents within 30 days prior to study entry or during active participation in the study (defined as from CAN-2409 injection until tumor progression).

Answer: C