Radiation Therapy Combined With Chemotherapy in Treating Patients With Anaplastic Astrocytoma or Mixed Gliomas

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00004259
First received: January 28, 2000
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as temozolomide, carmustine, and lomustine, use 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 randomized phase III trial is studying radiation therapy and temozolomide to see how well they work compared to radiation therapy and carmustine or lomustine in treating patients with anaplastic astrocytoma or mixed gliomas.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: Nitrosourea (BCNU or CCNU)
Drug: temozolomide
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Study (Phase I Closed) of Radiation Therapy and Temozolomide Versus Radiation Therapy and Nitrosourea for Anaplastic Astrocytoma And Mixed Anaplastic Oligoastrocytoma (Astrocytoma Dominant)

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Overall survival (OS) [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after 155 deaths have been reported. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to tumor progression (TTP) [ Time Frame: From randomization to date of progression, death, or last follow-up. Analysis occurs at the same time as the primary outcome analysis. ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: From start of treatment to end of follow-up. Analysis occurs at the same time as the primary outcome analysis. ] [ Designated as safety issue: Yes ]
  • Correlation of molecular analyses with OS and TTP [ Time Frame: Molecular markers are centrally reviewed after randomization. ] [ Designated as safety issue: No ]

Enrollment: 201
Study Start Date: June 2000
Estimated Primary Completion Date: March 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radiation therapy (RT) + temozolomide
Radiation therapy (RT) + temozolomide
Drug: temozolomide Radiation: radiation therapy
Experimental: RT + nitrosourea (BCNU or CCNU)
RT + nitrosourea (BCNU or CCNU)
Drug: Nitrosourea (BCNU or CCNU) Radiation: radiation therapy
Experimental: RT + BCNU + temozolomide
RT + BCNU + temozolomide
Drug: Nitrosourea (BCNU or CCNU) Drug: temozolomide Radiation: radiation therapy
Experimental: RT + BCNU 200mg/m2 + temozolomide
RT + BCNU 200mg/m2 + temozolomide
Drug: Nitrosourea (BCNU or CCNU) Drug: temozolomide Radiation: radiation therapy
Experimental: RT + BCNU 150mg/m2 + temozolomide
RT + BCNU 150mg/m2 + temozolomide
Drug: Nitrosourea (BCNU or CCNU) Drug: temozolomide Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

  • Compare the overall survival and time to tumor progression in patients with anaplastic astrocytoma or mixed gliomas treated with radiotherapy combined with temozolomide vs carmustine or lomustine vs temozolomide and carmustine (arm discontinued as of 8/15/02).
  • Compare the relative toxic effects of these regimens in these patients.
  • Correlate molecular analyses with overall survival and time to tumor progression in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 50 vs 50 and over), Karnofsky performance status (60-80% vs 90-100%), and prior surgery (biopsy only vs resection).

Phase I (closed as of 8/15/02)

  • Prior to initiating the randomization to 1 of 3 treatment arms in phase III, 15 patients are accrued to arm III. If 2 or more of the first 15 patients experience grade 3 or worse pulmonary toxicity OR if 5 or more of the first 15 patients experience grade 4-5 thrombocytopenia/neutropenia, then arm III treatment is discontinued.

Phase III

  • Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients undergo radiotherapy 5 days a week for 6 weeks. Patients receive oral temozolomide on days 1-5 of the first week of radiotherapy. Chemotherapy repeats every 4 weeks for a total of 12 courses.
    • Arm II: Patients undergo radiotherapy as in arm I. Patients receive carmustine IV or lomustine IV over 1-2 hours on days 1-3 of the first week of radiotherapy and a second course on days 56-58. Chemotherapy repeats every 8 weeks for a total of 6 courses.
    • Arm III (discontinued as of 8/15/02): Patients undergo radiotherapy as in arm I. Patients receive carmustine IV or lomustine IV over 3 hours on day 5 and oral temozolomide (2 hours after completion of carmustine or lomustine infusion) on days 1-5 of the first week of radiotherapy. Combination chemotherapy repeats every 8 weeks for 6 courses.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for phase I of the study and then a total of 454 patients (227 per treatment arm) will be accrued for phase III of the study within 4 years. (Phase I closed as of 8/15/02)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically proven unifocal anaplastic astrocytoma or mixed gliomas, including the following:

    • Anaplastic oligoastrocytoma
    • Mixed oligodendroglial/astrocytic tumors

      • Oligodendroglial component must be no greater than 25%
  • No vascular proliferation and necrosis
  • Increased cellularity, pleomorphism, and nuclear atypia allowed
  • No tumor predominantly located in the posterior fossa (i.e., brainstem or cerebellum)
  • Patients with prior biopsy proven low grade astrocytoma who now have anaplastic astrocytoma and have had no prior radiotherapy or chemotherapy also eligible
  • Study therapy must begin within 6 weeks of diagnosis
  • No spinal cord tumors, spinal drop metastases, or metastases to noncontiguous meninges

    • Pathologic evidence of local meningeal infiltration by underlying tumor allowed

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • At least 1 year

Hematopoietic:

  • Hemoglobin at least 10 g/dL
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 150,000/mm^3

Hepatic:

  • Bilirubin less than 2 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) less than 2 times ULN
  • Alkaline phosphatase less than 2 times ULN

Renal:

  • Blood urea nitrogen no greater than 25 mg/dL
  • Creatinine less than 1.5 times normal

Pulmonary:

  • No pre-existing lung disease that, in the investigator's opinion, would preclude administration of carmustine or lomustine or completion of therapy

Other:

  • No other major medical illness or psychiatric impairment that would preclude study compliance
  • No other malignancy within the past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
  • No known hypersensitivity to 1 of the components of carmustine, lomustine, temozolomide, dacarbazine, or any other nitrosourea
  • No active infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior biologic therapy

Chemotherapy:

  • See Disease Characteristics
  • No prior chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics
  • No prior radiotherapy to brain or head and neck

Surgery:

  • Not specified

Other:

  • No other concurrent anticancer treatment for anaplastic astrocytoma until a recurrence is detected
  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: NCT00004259

  Show 92 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Investigators
Study Chair: Susan M. Chang, MD University of California, San Francisco
Study Chair: Kurt A. Jaeckle, MD Mayo Clinic
Study Chair: Peter Bushunow, MD Lipson Cancer and Blood Center at Rochester General Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00004259     History of Changes
Other Study ID Numbers: RTOG-9813, CDR0000067512, ECOG-R9813, NCCTG-RTOG-9813
Study First Received: January 28, 2000
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
adult anaplastic astrocytoma
adult mixed glioma

Additional relevant MeSH terms:
Astrocytoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014