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

This study has suspended participant recruitment.
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: March 24, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: temozolomide (TMZ)
Radiation: radiotherapy
Drug: PCV
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 2 years post-registration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 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 event [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: Yes ]
  • Time to progression (eg, clinical progression, radiographic progression or neurocognitive progression) [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]

Estimated Enrollment: 520
Study Start Date: September 2009
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A - Radiotherapy followed by PCV

Patients undergo radiotherapy (RT) 5 days per week for approximately 6 - 7 weeks. The patient has a 4-6 week treatment break. Patients receive PCV chemotherapy for 6 cycles of six to seven week-long cycles. During each cycle of PCV chemotherapy, the patient receives the three medications that compose PCV chemotherapy as follows:

  1. Lomustine (also called CCNU 110 mg/m^2) orally on day 1 of each cycle
  2. Matulane (also called procarbazine 60 mg/m^2) orally on days 8 through 21 of each cycle
  3. Oncovin (also called vincristine 1.4 mg/m^2) by IV on days 8 and 29 of each cycle
Radiation: radiotherapy
59.4 Gy
Drug: PCV
CCNU (oral), vincristine (IV) and procarbazine (oral)
Active Comparator: Arm B - Radiotherapy + TMZ followed by TMZ
Patients receive radiotherapy five days per week. Radiation therapy is performed as 33 fractions of 1.8 Gy for a total dose of 59.4 Gy. Temozolomide is given as 75 mg/m^2 orally daily during Cycle 1 for seven days per week for about 6-7 weeks. Patients have a 4 week treatment break. Adjuvant temozolomide is given as 150 or 200 mg/m^2 orally on days 1-5 only of each cycle. Cycles are about 4 weeks long each. Temozolomide may be extended to 12 cycles if the patients shows acceptable tolerance and no evidence of progression.
Drug: temozolomide (TMZ)
oral
Radiation: radiotherapy
59.4 Gy
Experimental: Arm C - TMZ Alone
Patients receive temozolomide 150 or 200 mg/m^2 orally on days 1-5 only for each cycle. Cycles are about 4 weeks long each.
Drug: temozolomide (TMZ)
oral

Detailed Description:

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00887146

  Hide Study Locations
Locations
United States, Alaska
Providence Alaska Medical Center
Anchorage, Alaska, United States, 99508
United States, Arizona
Arizona Oncology-Deer Valley Center
Phoenix, Arizona, United States, 85027
Arizona Oncology Services Foundation
Scottsdale, Arizona, United States, 85260
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Colorado
The Medical Center of Aurora
Aurora, Colorado, United States, 80012
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224
Florida Hospital
Orlando, Florida, United States, 32803
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Iowa
McFarland Clinic PC-William R Bliss Cancer Center
Ames, Iowa, United States, 50010
Medical Oncology and Hematology Associates-West Des Moines
Clive, Iowa, United States, 50325
Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Iowa Oncology Research Association CCOP
Des Moines, Iowa, United States, 50309
Medical Oncology and Hematology Associates
Des Moines, Iowa, United States, 50314
Medical Oncology and Hematology Associates-Des Moines
Des Moines, Iowa, United States, 50309
Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Michigan
Bixby Medical Center
Adrian, Michigan, United States, 49221
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, United States, 49503
Saint Mary's Health Care
Grand Rapids, Michigan, United States, 49503
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
William Beaumont Hospital-Royal Oak
Royal Oak, Michigan, United States, 48073
Munson Medical Center
Traverse City, Michigan, United States, 49684
United States, Minnesota
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Fairview-Southdale Hospital
Edina, Minnesota, United States, 55435
Unity Hospital
Fridley, Minnesota, United States, 55432
Saint John's Hospital - Healtheast
Maplewood, Minnesota, United States, 55109
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, United States, 55109
Abbott-Northwestern Hospital
Minneapolis, Minnesota, United States, 55102
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
North Memorial Medical Health Center
Robbinsdale, Minnesota, United States, 55422
Mayo Clinic
Rochester, Minnesota, United States, 55905
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States, 55416
Metro-Minnesota CCOP
Saint Louis Park, Minnesota, United States, 55416
United Hospital
Saint Paul, Minnesota, United States, 55102
Saint Francis Regional Medical Center
Shakopee, Minnesota, United States, 55379
Regions Hospital
St. Paul, Minnesota, United States, 55101
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
Rice Memorial Hospital
Wilmar, Minnesota, United States, 56201
Minnesota Oncology and Hematology PA-Woodbury
Woodbury, Minnesota, United States, 55125
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Alegent Health Bergan Mercy Medical Center
Omaha, Nebraska, United States, 68124
Alegent Health Immanuel Medical Center
Omaha, Nebraska, United States, 68122
Alegent Health Lakeside Hospital
Omaha, Nebraska, United States, 68130
Missouri Valley Cancer Consortium CCOP
Omaha, Nebraska, United States, 68106
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Highland Hospital
Rochester, New York, United States, 14620
University of Rochester
Rochester, New York, United States, 14642
United States, North Dakota
Altru Cancer Center
Grand Forks, North Dakota, United States, 58201
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Columbus CCOP
Columbus, Ohio, United States, 43215
Mount Carmel Health Center West
Columbus, Ohio, United States, 43222
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
The Mark H Zangmeister Center
Columbus, Ohio, United States, 43219
Saint Ann's Hospital
Westerville, Ohio, United States, 43081
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Abington Memorial Hospital
Abington, Pennsylvania, United States, 19001
Lehigh Valley Hospital
Allentown, Pennsylvania, United States, 18105
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Greenville Health System Cancer Institute-Andrews
Greenville, South Carolina, United States, 29601
Greenville Health System Cancer Institute-Butternut
Greenville, South Carolina, United States, 29605
Greenville Health System Cancer Institute-Faris
Greenville, South Carolina, United States, 29605
Greenville Health System Cancer Institute/Greenville CCOP
Greenville, South Carolina, United States, 29615
Cancer Centers of the Carolinas-Greer Medical Oncology
Greer, South Carolina, United States, 29650
Greenville Health System Cancer Institute-Seneca
Seneca, South Carolina, United States, 29672
Greenville Health System Cancer Institute-Spartanburg
Spartanburg, South Carolina, United States, 29307
United States, South Dakota
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57701
United States, Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
University of Texas Medical Branch
Galveston, Texas, United States, 77555
UTMB Cancer Center at Victory Lakes
League City, Texas, United States, 77573
United States, Utah
Sandra L Maxwell Cancer Center
Cedar City, Utah, United States, 84720
Intermountain Medical Center
Murray, Utah, United States, 84157
Utah Valley Regional Medical Center
Provo, Utah, United States, 84604
Dixie Medical Center Regional Cancer Center
Saint George, Utah, United States, 84770
LDS Hospital
Salt Lake City, Utah, United States, 84143
Utah Cancer Specialists-Salt Lake City
Salt Lake City, Utah, United States, 84106
United States, Washington
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, United States, 98225
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
United States, Wisconsin
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States, 54601
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Waukesha Memorial Hospital
Waukesha, Wisconsin, United States, 53188
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
European Organisation for Research and Treatment of Cancer - EORTC
Radiation Therapy Oncology Group
Investigators
Study Chair: Kurt A. Jaeckle, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00887146     History of Changes
Other Study ID Numbers: NCCTG-N0577, NCI-2011-01915, EORTC-26081-22086, EudraCT-2008-007295-14, CDR0000640442
Study First Received: April 22, 2009
Last Updated: March 24, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015