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

NCT ID: NCT01372774

Last Updated: 2022-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 194 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2019-12-15

Brief Summary

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.

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.

Conditions

Radiation Toxicity; Cognitive/Functional Effects; Metastatic Cancer; Neurotoxicity; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

whole-brain radiation therapy

Intervention Type: RADIATION

Undergo radiotherapy (RT)

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.

Group Type: EXPERIMENTAL

stereotactic radiosurgery

Intervention Type: RADIATION

Undergo RT

Interventions

stereotactic radiosurgery

Undergo RT

Intervention Type: RADIATION

whole-brain radiation therapy

Undergo radiotherapy (RT)

Intervention Type: RADIATION

Eligibility Criteria

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.

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul D. Brown, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

Mills - Peninsula Hospitals

Burlingame, California, United States

Los Angeles County-USC Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Mount Sinai Medical Center

Miami Beach, Florida, United States

John B Amos Cancer Center

Columbus, Georgia, United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Memorial Hospital of South Bend

South Bend, Indiana, United States

Lowell General Hospital

Lowell, Massachusetts, United States

Saint Vincent Hospital/Reliant Medical Group

Worcester, Massachusetts, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Sanford Clinic North-Bemidji

Bemidji, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Regions Hospital

Saint Paul, Minnesota, United States

United Hospital

Saint Paul, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Wentworth-Douglass Hospital

Dover, New Hampshire, United States

Somerset Medical Center

Somerville, New Jersey, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States

Sanford Clinic North-Fargo

Fargo, North Dakota, United States

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

Saint Luke's University Hospital-Bethlehem Campus

Bethlehem, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Aria Health-Torresdale Campus

Philadelphia, Pennsylvania, United States

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

University of Texas Medical Branch

Galveston, Texas, United States

Saint Vincent Hospital

Green Bay, Wisconsin, United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Huntoon K, Anderson SK, Ballman KV, Twohy E, Dooley K, Jiang W, An Y, Li J, von Roemeling C, Qie Y, Ross OA, Cerhan JH, Whitton AC, Greenspoon JN, Parney IF, Ashman JB, Bahary JP, Hadjipanayis C, Urbanic JJ, Farace E, Khuntia D, Laack NN, Brown PD, Roberge D, Kim BYS. Association of circulating markers with cognitive decline after radiation therapy for brain metastasis. Neuro Oncol. 2023 Jun 2;25(6):1123-1131. doi: 10.1093/neuonc/noac262.

Reference Type: DERIVED

PMID: 36472389 (View on PubMed)

Palmer JD, Klamer BG, Ballman KV, Brown PD, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, Greenspoon J, Parney IF, Laack NNI, Ashman JB, Bahary JP, Hadjipanayis CG, Urbanic JJ, Barker FG 2nd, Farace E, Khuntia D, Giannini C, Buckner JC, Galanis E, Roberge D. Association of Long-term Outcomes With Stereotactic Radiosurgery vs Whole-Brain Radiotherapy for Resected Brain Metastasis: A Secondary Analysis of The N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group) Randomized Clinical Trial. JAMA Oncol. 2022 Dec 1;8(12):1809-1815. doi: 10.1001/jamaoncol.2022.5049.

Reference Type: DERIVED

PMID: 36264568 (View on PubMed)

Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, Greenspoon J, Parney IF, Laack NNI, Ashman JB, Bahary JP, Hadjipanayis CG, Urbanic JJ, Barker FG 2nd, Farace E, Khuntia D, Giannini C, Buckner JC, Galanis E, Roberge D. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1049-1060. doi: 10.1016/S1470-2045(17)30441-2. Epub 2017 Jul 4.

Reference Type: DERIVED

PMID: 28687377 (View on PubMed)

Related Links

https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Other Identifiers

NCCTG-N107C

Identifier Type: -

Identifier Source: secondary_id

CDR0000701474

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2011-02676

Identifier Type: REGISTRY

Identifier Source: secondary_id

N107C

Identifier Type: -

Identifier Source: org_study_id