Radiation Therapy (RT) and Temozolomide (TMZ) in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Gliosarcoma; Central Nervous System Neoplasms
Intervention: Concurrent temozolomide; Concurrent radiation therapy; 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle; 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle
Intervention description: Daily oral temozolomide (75 mg/m2) up to 49 doses.; 60 Gy in 2 Gy fractions; Oral temozolomide on days 1-5 of a 28-day cycle. Dose starts at 150mg/m2 for first cycle, increases to 200mg/m2 for subsequent cycles if no unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive up to 6 more courses of temozolomide.; Oral temozolomide on days 1-21 of a 28-day cycle. Dose starts at 75mg/m2 for first cycle, increases to 100mg/m2 for subsequent cycles if no unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive up to 6 more courses of temozolomide.
Intervention MeSH terms: Temozolomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1173.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma

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. Giving radiation therapy
      together with temozolomide may kill more tumor cells. It is not yet known which schedule of
      temozolomide when given together with radiation therapy is more effective in treating
      glioblastoma or gliosarcoma.

      PURPOSE: This randomized phase III trial is studying two different schedules of temozolomide
      to compare how well they work when given together with radiation therapy in treating patients
      with newly diagnosed glioblastoma or gliosarcoma.
    

Eligibility criteria:

        Inclusion criteria:

          1. Histopathologically proven diagnosis of glioblastoma. Since gliosarcoma is a variant
             of glioblastoma, gliosarcoma is also an eligible diagnosis.

          2. Patients must have at least 1 block of tissue available for analysis of MGMT status;
             fresh frozen tumor tissue acquisition is encouraged.

          3. Diagnosis must be established by open biopsy or tumor resection. Patients who have
             only had a stereotactic biopsy are not eligible.

          4. The tumor must have a supratentorial component.

          5. Patients must have recovered from the effects of surgery, postoperative infection, and
             other complications before study registration.

          6. A diagnostic contrast-enhanced magnetic resonance imaging (MRI) or computerized
             tomography (CT) scan (if MRI is not available) of the brain must be performed
             preoperatively and postoperatively. The postoperative scan must be done within 28 days
             of registration and prior to the initiation of radiotherapy. Preoperative and
             postoperative scans must be the same type. If CT scans were performed perioperatively,
             a CT and an MRI should be performed before randomization.

             6.1. Patients unable to undergo MRI imaging because of non-compatible devices can be
             enrolled, provided pre- and post-operative contrast-enhanced CT scans are obtained and
             are of sufficient quality.

          7. Therapy must begin ≤ 5 weeks after the most recent brain tumor surgery.

          8. History/physical examination within 14 days prior to study registration.

          9. Neurologic examination within 14 days prior to study registration.

         10. Documentation of steroid doses within 14 days prior to study registration and stable
             or decreasing steroid dose within 5 days prior to registration.

         11. Karnofsky performance status of ≥ 60.

         12. Age ≥ 18 years.

         13. Complete blood count (CBC)/differential obtained within 14 days prior to study
             registration, with adequate bone marrow function as defined below: 13.1 Absolute
             neutrophil count (ANC) ≥ 1500 cells/mm3. 13.2 Platelets ≥ 100,000 cells/mm3. 13.3
             Hemoglobin ≥ 10 g/dl. (Note: The use of transfusion or other intervention to achieve
             Hgb ≥ 10 g/dl is acceptable.)

         14. Adequate renal function, as defined below:

             14.1 Blood urea nitrogen (BUN) ≤ 25 mg/dl within 14 days prior to study registration
             14.2 Creatinine ≤ 1.7 mg/dl within 14 days prior to study registration

         15. Adequate hepatic function, as defined below:

             15.1 Bilirubin ≤ 2.0 mg/dl within 14 days prior to study registration 15.2 Alanine
             aminotransferase (ALT) ≤ 3 x normal range within 14 days prior to study registration
             15.3 Aspartate aminotransferase (AST) ≤ 3 x normal range within 14 days prior to study
             registration

         16. Patients must sign a study-specific informed consent prior to study registration.

             If the patient's mental status precludes his/her giving informed consent, written
             informed consent may be given by the responsible family member.

         17. For females of child-bearing potential, negative serum pregnancy test within 72 hours
             prior to starting temozolomide.

         18. Women of childbearing potential and male participants must practice adequate

        Exclusion criteria:

          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).

          2. Recurrent or multifocal malignant gliomas

          3. Metastases detected below the tentorium or beyond the cranial vault.

          4. Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note
             that prior chemotherapy for a different cancer is allowable. Prior use of Gliadel
             wafers or any other intratumoral or intracavitary treatment are not permitted. See
             Section 1.

          5. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in
             overlap of radiation fields.

          6. Severe, active co-morbidity, defined as follows:

               -  6.1. Unstable angina and/or congestive heart failure requiring hospitalization.

               -  6.2. Transmural myocardial infarction within the last 6 months.

               -  6.3. Acute bacterial or fungal infection requiring intravenous antibiotics at the
                  time of registration.

               -  6.4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory
                  illness requiring hospitalization or precluding study therapy at the time of
                  registration.

               -  6.5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation
                  defects; note, however, that laboratory tests for liver function and coagulation
                  parameters are not required for entry into this protocol.

               -  6.6. Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for
                  Disease Control and Prevention (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 may be significantly immunosuppressive.

               -  6.7. Major medical illnesses or psychiatric impairments that in the
                  investigator's opinion will prevent administration or completion of protocol
                  therapy.

               -  6.8. 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.

          7. Pregnancy or 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 treatment involved in this study may be significantly
             teratogenic.

          8. Pregnant or lactating women, due to possible adverse effects on the developing fetus
             or infant due to study drug;

          9. Prior allergic reaction to temozolomide.

         10. Patients treated on any other therapeutic clinical protocols within 30 days prior to
             study entry or during participation in the study.

         11. No tissue provided for histopathologic central review and MGMT status.

         12. Tissue provided by stereotactic biopsy method.