Stereotactic Radiosurgery or Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases That Have Been Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01372774
First received: June 11, 2011
Last updated: August 10, 2015
Last verified: August 2015
  Purpose

RATIONALE: Stereotactic radiosurgery may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether stereotactic radiosurgery is more effective than whole-brain radiation therapy in treating patients with brain metastases that have been removed by surgery.

PURPOSE: This randomized phase III trial studies how well stereotactic radiosurgery works compared to whole-brain radiation therapy in treating patients with brain metastases that have been removed by surgery.


Condition Intervention Phase
Cognitive/Functional Effects
Metastatic Cancer
Neurotoxicity
Radiation Toxicity
Unspecified Adult Solid Tumor, Protocol Specific
Radiation: stereotactic radiosurgery
Radiation: whole-brain 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 Trial of Post-Surgical Stereotactic Radiosurgery (SRS) Compared With Whole Brain Radiotherapy (WBRT) for Resected Metastatic Brain Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Neurocognitive progression at 6 months post-radiation in patients who received SRS compared to patients who received WBRT [ Time Frame: Up to 6 months post radiation ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 6 months post radiation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Local control of the surgical bed [ Time Frame: Up to 6 months post radiation ] [ Designated as safety issue: No ]
  • Time to CNS failure in these patients [ Time Frame: Up to 6 months post radiation ] [ Designated as safety issue: No ]
  • Quality-of-life at 6 months of these patients [ Time Frame: Up to 6 months post randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 192
Study Start Date: July 2011
Estimated Primary Completion Date: March 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I - WBRT
Patients undergo whole brain radiotherapy (WBRT) once a day, 5 days a week, for approximately 3 weeks. Patient observation/follow up occurs at week 12 and months 6, 9, 12, 16 and 24 post registration/randomization. Event monitoring occurs every 6 months until 5 years post registration/randomization.
Radiation: whole-brain radiation therapy
Undergo radiotherapy (RT)
Experimental: Arm II - SRS
Patients undergo stereotactic radiosurgery (SRS) using a gamma knife or a linear accelerator procedure. Patient observation/follow up occurs at week 12 and months 6, 9, 12, 16 and 24 post registration/randomization. Event monitoring occurs every 6 months until 5 years post registration/randomization.
Radiation: stereotactic radiosurgery
Undergo RT

Detailed Description:

Primary Goals

  1. Overall Survival - To determine in patients with one to four brain metastases whether there is improved overall survival in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
  2. Neurocognitive Progression - To determine in patients with one to four brain metastases whether there is less neurocognitive progression post-randomization in patients who receive SRS to the surgical bed compared to patients who receive WBRT.

Secondary Goals

  1. Quality of Life (QOL) - To determine in patients with resected brain metastases whether there is improved QOL in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
  2. Central Nervous System Failure - To determine in patients with one to four brain metastases whether there is equal or longer time to central nervous system (CNS) failure (brain) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
  3. Functional Independence - To determine in patients with one to four brain metastases whether there is longer duration of functional independence in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
  4. Long-Term Neurocognitive Status - To determine in patients with one to four brain metastases whether there is better long-term neurocognitive status in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
  5. Adverse Events - To tabulate and descriptively compare the post-treatment adverse events associated with the interventions.
  6. Local Tumor Bed Recurrence - To evaluate local tumor bed recurrence at 6 months with post-surgical SRS to the surgical bed in comparison to WBRT.
  7. Local Recurrence - To evaluate time to local recurrence with post-surgical SRS to the surgical bed in comparison to WBRT.
  8. CNS Failure Patterns - To evaluate if there is any difference in CNS failure patterns (local, distant, leptomeningeal) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.

OUTLINE: This is a multicenter study. Patients are stratified according to age in years (< 60 vs ≥ 60), extracranial disease controlled (≤ 3 months vs > 3 months), number of pre-operative brain metastases (1 vs 2-4), histology (lung vs radioresistant [brain metastases from a sarcoma, melanoma, or renal cell carcinoma histology] vs other), and resection cavity maximal diameter (≤ 3 cm vs > 3 cm). Patient must complete baseline QOL and neurocognitive tests prior to registration/randomization. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo whole-brain radiotherapy (WBRT) once a day, 5 days a week, for approximately 3 weeks.
  • Arm II: Patients undergo stereotactic radiosurgery (SRS) using a gamma knife or a linear accelerator procedure.

Event monitoring occurs up to 5 years post registration/randomization.

  Eligibility

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

Pre-registration Inclusion Criteria:

  1. Number of Brain Metastases - Four or fewer brain metastases (as defined on the pre-operative MRI or CT brain scan) and status post resection of one of the lesions.
  2. Non-CNS Primary Site - Pathology from the resected brain metastasis must be consistent with a non-central nervous system primary site. Note: Patients with or without active disease outside the nervous system are eligible (including patients with unknown primaries), as long as the pathology from the brain is consistent with a non-central nervous system primary site.
  3. Size of Metastases - Any unresected lesions must measure < 3.0 cm in maximal extent on the contrasted MRI or CT brain scan obtained ≤ 35 days prior to pre-registration. The unresected lesions will be treated with SRS as outlined in the treatment section of the protocol. Note: The metastases size restriction does not apply to the resected brain metastasis; with resected brain metastases only surgical cavity size determines eligibility.
  4. Size of Resection Cavity - Resection cavity must measure <5.0 cm in maximal extent on the post-operative MRI or CT brain scan obtained ≤35 days prior to pre-registration.

    Note: It is permissible for the resection of a dominant brain metastasis to include a smaller "satellite" metastasis as long as the single resection cavity is less than the maximum size requirements.

  5. Tumor Staging Procedures - All standard tumor-staging procedures necessary to define baseline extra cranial disease status completed ≤42 days prior to pre-registration.
  6. Treatment with Gamma Knife or Radiosurgery - Able to be treated with either a gamma knife or a linear accelerator-based radiosurgery system.
  7. Age ≥ 18 years
  8. Neurocognitive Testing - Willing and able to complete neurocognitive testing without assistance from family and companions. Note: Because neurocognitive testing is one of the primary goals of this study, patients must be able to utilize English language booklets (and/or French booklets if enrolled in Canada).
  9. Quality of Life (QOL) Questionnaires - Willing and able to complete QOL by themselves or with assistance
  10. ECOG Performance Status - ECOG Performance Status (PS) 0, 1, or 2.
  11. SRS Credentialed by IROC Houston Quality Assurance - The site's SRS facility is IROC Houston Quality Assurance approved.
  12. Neurocognitive Testing Credentialing - The site study team member performing neurocognitive testing of patients must have credentialing confirming completion of the neurocognitive testing training of the protocol.
  13. Written Informed Consent - Provide written informed consent
  14. Mandatory Samples for Correlative Tests - Willing to provide mandatory blood and urine samples for correlative research purposes.

Pre-registration Exclusion Criteria:

  1. Pregnancy, Nursing and Contraception - pregnant women, nursing women and men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment.
  2. Prior Cranial Radiation Therapy
  3. MRI or CT Scans - Inability to complete a MRI or CT scan with contrast of the head.
  4. Gadolinium Allergy - Known allergy to gadolinium.
  5. Cytotoxic Chemotherapy - Planned cytotoxic chemotherapy during the SRS or WBRT.
  6. Other Tumor Types - Primary germ cell tumor, small cell carcinoma, or lymphoma
  7. Leptomeningeal Metastasis - Widespread definitive leptomeningeal metastasis
  8. Location of Brain Metastasis - A brain metastasis that is located ≤ 5 mm of the optic chiasm or within the brainstem.

Randomization Inclusion Criteria:

  1. Number of Unresected Lesions - Post-operative MRI or CT scan confirmed zero, one, two or three unresected lesions.

    1.1 Each unresected lesion must measure ≤ 3.0 cm in maximal extent on the contrasted post-operative MRI or CT brain scan.

    1.2 Note: The pre-registration, post-operative, brain scan may be used for the randomization scan if obtained ≤ 28 days prior to randomization.

    1.3 Note: If there are no unresected brain metastases (i.e., all brain metastases have been resected), a post-operative CT brain scan may be used if obtained ≤ 28 days prior to randomization.

  2. Size of Resection Cavity - Post-operative MRI or CT scan confirms resection cavity measures < 5.0 cm in maximal extent.

    2.1 Note: The pre-registration, post-operative brain scan may be used for the randomization scan if obtained ≤ 28 days prior to randomization.

    2.2 Note: If there are no unresected brain metastases (i.e., all brain metastases have been resected), a post-operative CT brain scan may be used if obtained ≤28 days prior to randomization.

  3. Urine or Serum Pregnancy Test - Negative urine or serum pregnancy test done ≤ 7 days prior to randomization, for women of child bearing potential only.

Randomization Exclusion Criteria: none

  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: NCT01372774

Contacts
Contact: Paul Brown, MD (713) 563-2415

  Show 37 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Paul D. Brown, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01372774     History of Changes
Other Study ID Numbers: N107C, NCCTG-N107C, CDR0000701474, NCI-2011-02676
Study First Received: June 11, 2011
Last Updated: August 10, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
neurotoxicity
radiation toxicity
cognitive/functional effects
tumors metastatic to brain
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasm Metastasis
Neurotoxicity Syndromes
Radiation Injuries
Chemically-Induced Disorders
Neoplasms
Neoplastic Processes
Nervous System Diseases
Pathologic Processes
Poisoning
Wounds and Injuries

ClinicalTrials.gov processed this record on August 27, 2015