Details

Details

Title Phase III Intergroup Study of Temozolomide Alone versus Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy with Adjuvant PCV Chemotherapy in Patients with 1p/19q Co-deleted Anaplastic Glioma

IRB NCTG1310

CC CC00039; N0577

Hospital Fairview, Hillcrest, Main Campus, Mansfield, Wooster

Stage N/A

Phase Phase 3

Disease Brain

Drug Temozolomide

Description

Description

Primary Goal
  • To determine whether patients who receive radiotherapy with concomitant temozolomide followed by adjuvant temozolomide (RT + TMZ → TMZ) (ARM B) have a marginally better progression free survival (PFS) as compared with patients who receive radiotherapy followed by adjuvant PCV chemotherapy (RT → PCV) (ARM A).
Secondary Goals
  • To determine whether patients who receive RT + T MZ → TMZ have a significantly longer time to progression (clinical or radiographic progression) as compared with patients who receive radiotherapy followed by adjuvant PCV chemotherapy (RT → PCV).
  • To determine whether there is a difference in survival based on translocation status and MGMT promoter hypermethylation status.
  • To perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life.
  • To determine the toxicity of the treatment in each arm and perform descriptive comparisons.
  • To determine the neurocognitive and QOL effects in patients treated on this protocol and correlate these results with outcome endpoints.
  • To store blood products (i.e., plasma, DNA, and buffy coat), tumor tissue and MRI/CT images for future scientific investigations.
Inclusion Criteria

Inclusion Criteria

  1. Central pathology review submission is mandatory prior to registration to confirm eligibility. Patients must be willing to submit tissue samples for mandatory central pathology review submission (see Section 17.2) and deletion status determination (see Section 17.51). It should be initiated as soon after surgery as possible.
  2. Age ≥ 18 years of age.
  3. Newly diagnosed and ≤ 3 months from surgical diagnosis
  4. Histological confirmation of anaplastic glioma or low grade glioma. Histological confirmation of anaplastic glioma (oligodendroglioma, mixed, or astrocytoma [(WHO grade 2 or 3]) or low grade glioma (WHO grade 2), as determined by pre-registration central pathology review. Note: Mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q.
  5. Patients with codeleted low grade gliomas must also be considered "high risk" by clinical criteria utilized in RTOG 9802 and must be either:
    • Age ≥ 40 and any surgical therapy
    • Age < 40 and subtotal resection or biopsy
  6. Tumor tissue must show co-deletetion for the relevant portions of chromosomes 1p and 19q by FISH analysis, as defined by the testing laboratory.
  7. Surgery (partial or gross total resection or biopsy) must be performed ≥ 2 weeks prior to registration; patient must have recovered from the effects of surgery.
  8. The following laboratory values obtained ≤ 21 days prior to registration.
    • Absolute neutrophil count (ANC) ≥1500 /mm3
    • Platelet (PLTs) count ≥100,000 / mm3
    • Hemoglobin (Hgb) > 9.0 g/dL
    • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
    • SGOT (AST) ≤ 3 x ULN
    • Creatinine ≤ 1.5 x ULN
  9. Negative serum or urine pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
  10. Willing and able to complete neurocognitive testing without assistance and the QOL by themselves or with assistance (see Section 4.3).
  11. ECOG performance status (PS) of 0, 1 or 2 (See Appendix I).
  12. Provide informed written consent.
  13. Willing to return to enrolling institution for follow-up during the Active Monitoring Phase (that is, the active treatment and observation portion) of the study)
  14. Patient willing to provide tissue samples for correlative research purposes (see Sections 6.17, 17.3, and 17.52-17.53).
Exclusion Criteria

Exclusion Criteria

  1. Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception during this study and for up to 6 months following the completion of temozolomide treatments.
  2. Received any prior surgery, radiation therapy or chemotherapy for any CNS neoplasm. Note: Patients who have had a prior low grade glioma with/without surgery and who now have anaplastic glioma with no prior radiation or chemotherapy are eligible for the study.
  3. Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
  4. Concomitant serious immunocompromised status (other than that related to concomitant steroids) that would compromise the safety of the patient on the study.
  5. Patients known to be HIV positive and currently receiving retroviral therapy. Note: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for the study
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  7. Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm.
  8. Other active malignancy within 5 years of registration. Exceptions: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. Note: If there is a history of prior malignancy, the patient must not be receiving other specific treatment (other than hormonal therapy) for their cancer.
  9. History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
  10. Recent history of hepatitis infection or treating physician determined that the patient would be at significant risk of reactivation of hepatitis.