Radiation Therapy With Concomitant and Adjuvant Temozolomide or Radiation Therapy With Adjuvant PCV or Temozolomide Alone in Treating Patients With Anaplastic Glioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborators:
European Organisation for Research and Treatment of Cancer - EORTC
Radiation Therapy Oncology Group
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00887146
First received: April 22, 2009
Last updated: November 7, 2013
Last verified: November 2013

April 22, 2009
November 7, 2013
October 2009
December 2018   (final data collection date for primary outcome measure)
Progression-free survival [ Time Frame: Up to 2 years post-registration ] [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Time to event (i.e., clinical progression, neurocognitive progression, and radiographic progression) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00887146 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]
  • Time to progression (i.e., clinical progression, neurocognitive progression, and radiographic progression) [ Time Frame: Up to 2 years post-registration ] [ Designated as safety issue: No ]
  • Objective tumor response [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]
  • Treatment-related adverse events according to NCI CTCAE v. 3 [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: Yes ]
  • Progression-free survival at 6, 12, and 24 months [ Designated as safety issue: No ]
  • Objective tumor response [ Designated as safety issue: No ]
  • Treatment-related adverse events according to NCI CTCAE v.3 [ Designated as safety issue: Yes ]
  • Interphase fusion of the CEP1 probe and a 19p12 probe to detect the t(1:19) in paraffin-embedded tumor sections by FISH [ Designated as safety issue: No ]
  • Associations between clinical outcomes (survival, progression-free survival, and objective response) and MGMT methylation status [ Designated as safety issue: No ]
  • Additional known prognostic markers, including but not limited to PTEN, EGFR, EGFRvIII, p53, and any additional markers which are known or are identified during the course of this study that are considered relevant by the study investigators and thei ... [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Radiation Therapy With Concomitant and Adjuvant Temozolomide or Radiation Therapy With Adjuvant PCV or Temozolomide Alone in Treating Patients With Anaplastic Glioma
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

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 giving temozolomide alone, radiation followed by PCV, or temozolomide together with radiation therapy followed by temozolomide is more effective in treating anaplastic glioma.

This research study is a Phase III clinical trial. The purpose of this study is to compare the effectiveness of radiotherapy with temozolomide followed by temozolomide chemotherapy versus radiotherapy followed by PCV chemotherapy versus temozolomide chemotherapy alone in the treatment of anaplastic glioma. Patients are stratified according to cooperative group (EORTC vs North American groups [NCCTG, RTOG, CTSU, and NCIC CTG]), age (≤ 50 years vs > 50 years), and ECOG performance score (0 or 1 vs 2). Patients are randomized to 1 of 3 treatment arms. Please see the "Arms" section below for more detailed information. The primary and secondary objectives are summarized below.

Objectives:

Primary Objective:

To determine whether patients who receive radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant temozolomide (RT + TMZ --> TMZ) have a marginally better progression free survival (PFS) than patients who receive radiotherapy followed by PCV chemotherapy (RT --> PCV).

Secondary Objectives:

  1. Time to Progression - To determine whether patients who receive temozolomide (TMZ) alone have a significantly longer time to progression (neurocognitive, clinical or radiographic progression) than patients who receive radiotherapy with concomitant TMZ followed by adjuvant TMZ (RT + TMZ --> TMZ) or radiotherapy followed by PCV chemotherapy (RT --> PCV).
  2. Survival Difference - Determine whether there is a difference in survival based on translocation status and MGMT promoter hypermethylation status.
  3. Descriptive Comparisons of Additional Secondary Endpoints - Perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life.
  4. Toxicity - Determine the toxicity of the treatment in each arm and perform descriptive comparisons.
  5. Descriptive Determination of Timing of RT - Determine descriptively whether it is reasonable to delay RT in this patient cohort by documenting the time to progression and progression free survival of patients receiving temozolomide alone
  6. Neurocognitive and Quality of Life (QOL) Effects - Determine the neurocognitive and QOL effects in patients treated on this protocol and correlate these results with outcome endpoints

After completion of study therapy, patients are followed every 12 weeks for 1 year, then every 4 months for 2 years and then every 6 months until progressive disease.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
  • Drug: Temozolomide (TMZ)
    Patients receive oral temozolomide.
  • Radiation: Radiotherapy
    Patients undergo radiotherapy performed as 33 fractions of 1.8 Gy for a total dose of 59.4 Gy.
  • Drug: PCV - Procarbazine + CCNU + Vincristine
    Patients receive PCV chemotherapy. On Day 1, CCNU 110 mg/m2 is administered orally. On Days 8 and 29, vincristine 1.4 mg/m2 is administered intravenously. And on Days 8-21, procarbazine 60 mg/m2 is administered orally. The course of treatment is repeated for a total of 6 cycles.
  • Active Comparator: Arm A - Radiotherapy followed by PCV
    Patients undergo radiotherapy (RT) 5 days per week for approximately 6 - 7 weeks in Cycle 1. The patient undergoes a rest period for approximately 4 weeks in Cycle 2. For Cycles 3-8, patients are administered PCV chemotherapy for about 6 - 7 weeks for each cycle in the absence of disease progression and unacceptable toxicity.
    Interventions:
    • Radiation: Radiotherapy
    • Drug: PCV - Procarbazine + CCNU + Vincristine
  • Experimental: Arm B - Radiotherapy + TMZ followed by TMZ
    Patients undergo radiation and temozolomide treatment daily for Cycle 1 for approximately 6-7 weeks. Patients receive temozolomide 75 mg/m2 orally. There is a rest period for approximately 4 weeks during Cycle 2. For Cycles 3-8, patients undergo adjuvant temozolomide 150 or 1200 mg/m2 orally on Days 1-5 of each cycle. Each cycle is approximately 4 weeks in duration. Temozolomide may be extended to 12 cycles if there is acceptable tolerance and no evidence of progression.
    Interventions:
    • Drug: Temozolomide (TMZ)
    • Radiation: Radiotherapy
  • Experimental: Arm C - TMZ
    Patients receive oral temozolomide 150 or 1200 mg/m2 once daily on days 1-5 of each cycle. Each cycle is approximately 4 weeks. Patients undergo treatment for a total of 12 cycles in the absence of disease progression or unacceptable toxicity.
    Intervention: Drug: Temozolomide (TMZ)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
520
Not Provided
December 2018   (final data collection date for primary outcome measure)

Pre-Registration Inclusion Criteria:

Central Pathology Review Submission This review is mandatory prior to registration to confirm eligibility. Patients must be willing to submit tissue samples for mandatory central pathology review submission and deletion status determination. It should be initiated as soon after surgery as possible.

Registration Inclusion Criteria:

  1. Age ≥ 18 years
  2. Newly diagnosed and ≤ 3 months from surgical diagnosis
  3. Histological confirmation of anaplastic glioma (oligodendroglioma, mixed, or astrocytoma [WHO grade III], 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.
  4. Tumor is co-deleted for 1p and 19q.
  5. 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.
  6. The following laboratory values obtained ≤ 21 days prior to registration.

    1. Absolute neutrophil count (ANC) ≥ 1500/mm3
    2. Platelet (PLTs) count ≥ 100,000/mm3
    3. Hemoglobin (Hgb) > 9.0g/dL
    4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
    5. Serum glutamic oxaloacetic transaminase (SGOT) aspartate transaminase (AST) ≤ 3 x ULN
    6. Creatinine ≤ 1.5 x ULN
  7. Negative serum or urine pregnancy test done ≤ 7 days prior to registration for women of childbearing potential only.
  8. Willing and able to complete neurocognitive testing without assistance and the Quality of Life (QOL) questionnaires with or without assistance
  9. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  10. Provide informed written consent.
  11. Willing to return to enrolling institution for follow-up during the Active Monitoring Phase (ie, active treatment and observation portion of the study)
  12. Mandatory Tissue Samples for Correlative Research - Patient is willing to provide tissue samples for correlative research purposes

Registration Exclusion Criteria:

  1. 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 central nervous system (CNS) neoplasm. Note: Patients who have had a prior low grade glioma with or 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).
  5. Patients known to be Human Immunodeficiency Virus (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 which 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.
Both
18 Years and older
No
United States
 
NCT00887146
NCCTG-N0577, NCI-2011-01915, EORTC-26081-22086, EudraCT-2008-007295-14, CDR0000640442
Yes
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
  • National Cancer Institute (NCI)
  • European Organisation for Research and Treatment of Cancer - EORTC
  • Radiation Therapy Oncology Group
Study Chair: Kurt A. Jaeckle, MD Mayo Clinic
Alliance for Clinical Trials in Oncology
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP