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

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, Tissue collection/Repository, TreatmentTemporarily closed18 and overNCI, OtherNCCTG-N0577
NCI-2011-01915, EORTC-26081-22086, EudraCT-2008-007295-14, CDR0000640442, N0577, NCT00887146

Trial Description

Summary

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.

Further Study Information

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, 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 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

7. Banking of Biospecimens To bank blood products (i.e., plasma, DNA and buffy coat), tumor tissue and MRI/CT images for future scientific investigations

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 or until the end of study participation.

Eligibility Criteria

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/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

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.

Trial Contact Information

Trial Lead Organizations/Sponsors

Alliance for Clinical Trials in Oncology

  • National Cancer Institute
  • European Organization for Research and Treatment of Cancer
  • Radiation Therapy Oncology Group
Kurt A. Jaeckle, Study Chair

Trial Sites

U.S.A.

Iowa
Des Moines

CCOP - Iowa Oncology Research Association

Robert J Behrens
Ph: 515-282-2921

Maryland
Rockville

Cancer Trials Support Unit

Kurt A. Jaeckle

Nebraska
Omaha

CCOP - Missouri Valley Cancer Consortium

Gamini S. Soori
Ph: 402-991-8070ext202
Email: mwilwerding@mvcc.cc

Ohio
Columbus

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Kurt A. Jaeckle
Email: jaeckle.kurt@mayo.edu

Oregon
Gresham

Legacy Mount Hood Medical Center

Andrew Y Kee
Ph: 507-538-7623

Portland

Legacy Good Samaritan Hospital & Comprehensive Cancer Center

Andrew Y Kee
Ph: 507-538-7623

Washington
Seattle

CCOP - Virginia Mason Research Center

Craig R. Nichols
Ph: 503-215-6412
Email: vmmc.cancer_clinical_research@VirginiaMason.org

Austria

Vienna

Medical University of Vienna

Kurt A. Jaeckle

Belgium

Antwerpen

Alegemeen Ziekenhuis Middelheim

Kurt A. Jaeckle
Ph: 904-953-7102
Email: jaeckle.kurt@mayo.edu

France

Lyon

Centre Leon Berard

Kurt A. Jaeckle

Nice

Centre Antoine Lacassagne

Kurt A. Jaeckle
Ph: 904-953-7102
Email: jaeckle.kurt@mayo.edu

Villejuif

Institut Gustave Roussy

Kurt A. Jaeckle

Netherlands

Amsterdam

Academ Zienkenhuis Bij De University

Kurt A. Jaeckle

Groningen

University Medical Center Groningen

Kurt A. Jaeckle

Maastricht

University Hospital Maastricht

Kurt A. Jaeckle
Ph: 904-953-7102
Email: jaeckle.kurt@mayo.edu

Rotterdam

Erasmus University Medical Center

Kurt A. Jaeckle

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00887146
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.