Phase II Trial of Low-Dose Whole Brain Radiotherapy With Concurrent Temozolomide and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma Multiforme (GCC 1224)

This is an interventional treatment trial for Histologically Proven Diagnosis of Glioblastoma or Gliosarcoma (WHO Grade IV) focused on measuring GBM Read More

Inclusion Criteria:

• 3.1.1 Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV).

3.1.2 Infratentorial and multi-focal tumors are eligible. 3.1.3 History and physical with neurological examination, steroid documentation, height, and weight within 14 days of registration.

3.1.4 A diagnstic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy. The postoperative scan must be performed within 28 days prior to registration. (contrast enhanced Brain CT is allowed if MRI is contraindicated) 3.1.5 Karnofsky performance status ≥ 70 or ECOG performance status ≤ 2. 3.1.6 Age ≥ 18. 3.1.7 CBC with differential obtained within 14 days prior to registration, with adequate bone marrow function defined as follows:

• Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3.
• Platelets ≥ 100,000 cells/mm3.
• Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥10.0 g/dl is acceptable).

3.1.8 Adequate renal function within 14 days prior to registration, as defined below:

• BUN ≤ 30 mg/dl.
• Creatinine ≤ 1.7 mg/dl. 3.1.9 Adequate hepatic function within 14 days prior to registration, as defined below:
• Bilirubin ≤ 2.0 mg/dl.
• ALT/AST ≤ 3 x upper limit of normal (ULN). 3.1.10 Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to registration.

3.1.11 Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to registration. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:

• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
• In-range INR (between 2.5 and 3.5) on a stable dose of warfarin-based oral anticoagulant; or on a stable dose of low molecular weight heparin; or INR between 1.5 and 2 if a Greenfield filter is in place.

3.1.12 Patient must provide study specific informed consent prior to study entry.

3.1.13 For women of child-bearing potential, negative serum pregnancy test within 14 days prior to registration.

3.1.14 Women o f childbearing potential and male participants must practice adequate contraception.

Exclusion Criteria:

• 3.2.1 Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible.

3.2.2 Metastases beyond the cranial vault. 3.2.3 Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted.

3.2.4 Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in significant overlap of radiation fields.

3.2.5 Severe, active co-morbidity, defined as follows:

• Unstable angina and/or congestive heart failure within the last 6 months.
• Transmural myocardial infarction within the last 6 months.
• New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration.
• History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months.
• Serious and inadequately controlled cardiac arrhythmia.
• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
• Evidence of bleeding diathesis or coagulopathy.
• Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess, major surgical procedure or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection or follow-on craniotomies to manage complications of brain tumor management such as hemorrhage or infection.
• Bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol.
• Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol are significantly immunosuppressive.
• Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
• Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
• Cognitive impairment that precludes a patient from acting as his or her own agent to provide informed consent.

3.2.6 Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the chemotherapeutic treatment involved in this study is significantly teratogenic.

3.2.7 Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study treatment.

3.2.8 Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.

3.2.9 Inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker).