Trial record 1 of 1 for:    N0577
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Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborators:
National Cancer Institute (NCI)
European Organisation for Research and Treatment Center (EORTC)
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00887146
First received: April 22, 2009
Last updated: March 17, 2016
Last verified: March 2016

April 22, 2009
March 17, 2016
September 2009
December 2018   (final data collection date for primary outcome measure)
Progression-free survival [ Time Frame: Up to 5 years post-treatment ] [ 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-treatment ] [ Designated as safety issue: No ]
  • Objective tumor response [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
  • Treatment-related adverse event as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: Yes ]
  • Time to progression (eg, clinical progression, radiographic progression or neurocognitive progression) [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
  • 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 ]
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Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma
Phase III Intergroup Study of Radiotherapy With Concomitant and Adjuvant Temozolomide Versus Radiotherapy With Adjuvant PCV Chemotherapy in Patients With 1p/19q Co-deleted Anaplastic Glioma or Low Grade 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 radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.

This study will be a randomized phase III for patients with newly diagnosed co-deleted 1p/19q anaplastic glioma or high risk low grade glioma. The trial will only enroll patients with 1p/19q co-deletion. This study includes two arms as described in the "Arms" section. A dynamic allocation procedure will be used to allocate an equal number of patients to different arms (Arms A:B = 1:1). This procedure will balance the marginal distributions of the stratification factors among arms. The stratification factors that will be used are cooperative groups (EORTC vs. all North American groups), age (≤ 50 vs. > 50), performance score (ECOG 0-1 vs. 2), and tumor grade (anaplastic glioma vs. low grade glioma).

The primary goal is to determine whether patients who receive radiotherapy with concomitant temozolomide (TMZ) 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 PCV chemotherapy (RT --> PCV)(Arm A).

Secondary Goals:

  1. Time to Progression - To determine whether patients who receive (RT + TMZ --> 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).
  2. Correlation between exploratory biomarkers and survival - To determine whether there is a difference in survival based on t(1;19)(q10, p10) translocation status and MGMT promoter hypermethylation status.
  3. Descriptive Comparisons of Additional Secondary Endpoints - To perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life.
  4. Toxicity - To determine the toxicity of the treatment in each arm and perform descriptive comparisons.
  5. Neurocognitive and Quality of Life (QOL) Effects - To determine the neurocognitive and QOL effects in patients treated on this protocol and correlate these results with outcome endpoints.
  6. Banking of Biospecimens and Neuroimaging Studies - To store blood products (i.e., plasma, DNA and buffy coat), tumor tissue and MRI/CT images for future scientific investigations.

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

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
  • Drug: concomitant temozolomide (TMZ)
    75 mg/m^2, orally daily
  • Radiation: radiotherapy
  • Drug: procarbazine
    Days 8-21: 60 mg/m^2 orally
  • Drug: adjuvant temozolomide (TMZ)
    150 or 200 mg/m^2 orally
  • Drug: CCNU
    Day 1: 110 mg/m^2 orally
  • Drug: vincristine
    Days 8 and 29: 1.4 mg/m^2 IV
  • Active Comparator: Arm A - Radiotherapy followed by PCV

    Patients undergo radiotherapy (RT) 5 days per week for about 6-7 weeks. (Cycle 1 is about 6 to 7 weeks)

    Cycle 2 rest period is about 4 weeks.

    Patients receive PCV chemotherapy for about 6-7 weeks, a total of 6 cycles.

    Interventions:
    • Radiation: radiotherapy
    • Drug: procarbazine
    • Drug: CCNU
    • Drug: vincristine
  • Active Comparator: Arm B - Radiotherapy + TMZ followed by TMZ

    Patients undergo radiotherapy (RT) and temozolomide (TMZ) treatment for 5 days per week for about 6-7 weeks (Cycle 1).

    Cycle 2 rest period is about 4 weeks.

    Patients receive adjuvant temozolomide for about 4 weeks, a total of 6 cycles. TMZ may be extended to 12 cycles if the patient shows acceptable tolerance and no evidence of progression.

    Interventions:
    • Drug: concomitant temozolomide (TMZ)
    • Radiation: radiotherapy
    • Drug: adjuvant 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
360
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 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.
  4. 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 or age < 40 and subtotal resection or biopsy.
  5. Tumor tissue must show co-deletion for the relevant portions of chromosomes 1p and 19q by FISH analysis, as defined by the testing laboratory.
  6. 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.
  7. The following laboratory values obtained ≤ 21 days prior to registration.

    1. Absolute neutrophil count (ANC) ≥ 1500/mm^3
    2. Platelet (PLTs) count ≥ 100,000/mm^3
    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
  8. Negative serum or urine pregnancy test done ≤ 7 days prior to registration for women of childbearing potential only.
  9. Willing and able to complete neurocognitive testing without assistance and the Quality of Life (QOL) questionnaires with or without assistance
  10. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  11. Provide informed written consent.
  12. Willing to return to enrolling institution for follow-up during the Active Monitoring Phase (ie, active treatment and observation portion) of the study
  13. Mandatory Tissue Samples for Correlative Research -Patient willing to provide tissue samples for correlative research purposes

Registration Exclusion Criteria:

  1. Fetal/Newborn Toxicity: 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 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) that would compromise the safety of the patient on the study.
  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   (Adult, Senior)
No
Contact: Kurt Jaeckle, MD 904-953-7102
United States
Canada,   France,   Germany,   Netherlands
 
NCT00887146
Alliance N0577, NCI-2011-01915, EORTC-26081-22086, EudraCT-2008-007295-14, CDR0000640442
Yes
Not Provided
Not Provided
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
  • National Cancer Institute (NCI)
  • European Organisation for Research and Treatment Center (EORTC)
  • NCIC Clinical Trials Group
Study Chair: Kurt Jaeckle, MD Mayo Clinic
Alliance for Clinical Trials in Oncology
March 2016

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