Radiation Therapy, Temozolomide, and Irinotecan in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

A Phase II Study Of Radiation Therapy Plus Low Dose Temozolomide Followed By Temozolomide Plus Irinotecan For Glioblastoma Multiforme

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as temozolomide and irinotecan, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well radiation therapy, temozolomide, and irinotecan work in treating patients with newly diagnosed glioblastoma multiforme.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: irinotecan hydrochloride; Radiation: radiation therapy; Drug: temozolomide; Procedure: adjuvant therapy

Detailed Description

OBJECTIVES:

• Compare overall survival of patients with newly diagnosed supratentorial glioblastoma multiforme treated with radiotherapy and temozolomide followed by temozolomide and irinotecan with historical controls from the RTOG database.
• Determine the short- and long-term toxicity of this regimen in these patients.
• Determine progression-free survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Chemoradiotherapy: Patients undergo radiotherapy once daily, 5 days a week, for 6 weeks. Concurrently with radiotherapy, patients receive oral temozolomide once daily, 7 days a week, for 6 weeks.
• Post-radiotherapy chemotherapy: Beginning 4-6 weeks after the completion of chemoradiotherapy, patients receive irinotecan IV on days 1 and 15 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 157 patients will be accrued for this study within 11 months.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Foundation for Cancer Research and Education
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
    • Fresno, California, United States, 93720
      • Saint Agnes Medical Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Mission Hills, California, United States, 91346-9600
      • Providence Holy Cross Cancer Center
    • Pomona, California, United States, 91767
      • Pomona Valley Hospital Medical Center
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Inc.
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8032
      • Yale Comprehensive Cancer Center at Yale University School of Medicine
  • Delaware
    • Newark, Delaware, United States, 19718
      • CCOP - Christiana Care Health Services
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Shands Cancer Center
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Community Cancer Center
    • Rome, Georgia, United States, 30165
      • Regional Radiation Oncology Center at Rome
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Community Hospital
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Care Center at Ingalls Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Cancer Institute of Cape Girardeau
    • Springfield, Missouri, United States, 65802
      • CCOP - Cancer Research for the Ozarks
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
    • St Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center at Methodist Hospital - Omaha
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • Dartmouth - Hitchcock Concord
    • Lebanon, New Hampshire, United States, 03756
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cancer Institute of New Jersey at the Cooper University Hospital
    • Camden, New Jersey, United States, 08103
      • Cooper Cancer Institute
    • Edison, New Jersey, United States, 08818
      • John F. Kennedy Medical Center
    • Long Branch, New Jersey, United States, 07740
      • Monmouth Medical Center
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Research and Treatment Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14621
      • Lipson Cancer and Blood Center at Rochester General Hospital
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Randolph Hospital
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
    • Eden, North Carolina, United States, 27288
      • John Smith, Jr./Dalton McMichael Cancer Center at Morehead Memorial Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Greensboro, North Carolina, United States, 27401
      • Moses Cone Regional Cancer Center at Wesley Long Community Hospital
    • Reidsville, North Carolina, United States, 27320
      • Annie Penn Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Akron, Ohio, United States, 44304
      • Akron City Hospital
    • Alliance, Ohio, United States, 44601
      • Radiation Oncology Center
    • Canton, Ohio, United States, 44710
      • Aultman Hospital Cancer Center at Aultman Health Foundation
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Middletown, Ohio, United States, 45044
      • Middletown Regional Hospital
    • Salem, Ohio, United States, 44460
      • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
    • Troy, Ohio, United States, 45373
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Oregon
    • Glesham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
    • Portland, Oregon, United States, 97210
      • Comprehensive Cancer Center at Legacy Good Samaritan Hospital & Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center at Providence Portland Medical Center
    • Portland, Oregon, United States, 97227
      • Institute of Oncology at Vilnius University
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Allentown, Pennsylvania, United States, 18105
      • John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Hospital Cancer Center
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Cancer Center - Arnold Palmer Pavilion
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • McKeesport, Pennsylvania, United States, 15132
      • UPMC McKeesport
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburg, Pennsylvania, United States, 15213
      • Hillman Cancer Center at University of Pittsburgh Cancer Institute
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15219
      • Mercy Hospital of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Cancer Center at UPMC Presbyterian
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Cancer Center at Magee-Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15215
      • UPMC St. Margaret
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC - Shadyside
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC - Passavant Hospital
    • Pittsburgh, Pennsylvania, United States, 15243
      • Cancer Center at St. Clair Memorial Hospital
    • West Reading, Pennsylvania, United States, 19612
      • Reading Hospital and Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
    • York, Pennsylvania, United States, 17405
      • York Cancer Center at Wellspan Health
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Spartanburg, South Carolina, United States, 29304
      • CCOP - Upstate Carolina
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Utah
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84603
      • Utah Valley Regional Medical Center - Provo
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
    • St. George, Utah, United States, 84770
      • Dixie Regional Medical Center
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Green Mountain Oncology Group
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - University Health Center Campus
    • Rutland, Vermont, United States, 05701
      • Community Cancer Center at Rutland Regional Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Massey Cancer Center at Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Vancouver, Washington, United States, 98668
      • Southwest Washington Medical Center Cancer Center
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • St. Vincent Hospital
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Comprehensive Cancer Center
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed supratentorial glioblastoma multiforme by surgical biopsy or excision

  • No gliomas graded less than glioblastoma multiforme
  • No recurrent malignant gliomas
• No tumor foci below the tentorium or beyond the cranial vault
• Study therapy must begin ≤ 5 weeks after surgery

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• At least 8 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL*
• Hematocrit ≥ 30%* NOTE: *Transfusion allowed

Hepatic

• Bilirubin ≤ 0.5 mg/dL
• ALT or AST ≤ 2 times upper limit of normal

Renal

• Creatinine ≤ 1.5 mg/dL
• BUN ≤ 25 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 2 months after study participation
• No AIDS
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder
• No other major medical illness or psychiatric impairment that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent sargramostim (GM-CSF)

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• Concurrent steroid therapy allowed provided patient is on a stable or decreasing dose for at least 2 weeks before study entry

Radiotherapy

• No prior radiotherapy to the head or neck resulting in overlap of radiotherapy fields

  • Prior radiotherapy for stage T1 glottic cancer allowed

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• No enzyme-inducing antiepileptic drugs within 14 days before the initiation of irinotecan

  • Concurrent non-enzyme-inducing antiepileptic drugs allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RT with chemotherapy + post-radiation chemotherapy; Radiation therapy (RT) with concurrent chemotherapy + post-radiation chemotherapy	Drug: irinotecan hydrochloride; Radiation: radiation therapy; Drug: temozolomide; Procedure: adjuvant therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 18 months.

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	From randomization to date of progression, death, or last follow-up. Analysis occurs at the same time as the primary outcome analysis.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Christina I. Tsien, MD, University of Michigan Rogel Cancer Center

Publications and helpful links

General Publications

• Lieberman FS, Tsien C, Berkey B, et al.: Phase II trial of concomitant low dose temozolomide with external beam radiation (EBRT) followed by 12 months of temozolomide and irinotecan for newly diagnosed glioblastoma (GBM): preliminary results of RTOG 04-20. [Abstract] J Clin Oncol 24 (Suppl 18): A-1510, 2006.

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: December 8, 2004
• First Submitted That Met QC Criteria: December 8, 2004
• First Posted (Estimate): December 9, 2004

Study Record Updates

• Last Update Posted (Estimate): January 24, 2014
• Last Update Submitted That Met QC Criteria: January 23, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Temozolomide; Irinotecan
• Other Study ID Numbers: RTOG-0420; CDR0000389229