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

NCT01372774 | Completed Phase 3 Results DMC

• 4 other identifiers: N107CNCCTG-N107CCDR0000701474NCI-2011-02676
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 37

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.

Conditions

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

Keywords

neurotoxicity; radiation toxicity; cognitive/functional effects; tumors metastatic to brain; unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (2)

• Cognitive Deterioration Free Survival Post-radiation in Patients Who Received SRS Compared to Patients Who Received WBRT

  To determine in patients with one to four brain metastases whether there is less nuerocognitive progression post-randomization in patients who receive SRS to the surgical bed compared to patients who receive WBRT. Neurocognitive progression is defined as a drop of at least one stanard deviation from baseline in one of the six neurocognitive tests at post-randomization evaluation.

  from baseline up to 5 years post radiation

• 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. Overall survival is defined as the time from randomization to death from any cause.

  from baseline up to 5 years post radiation

Secondary Outcomes (3)

• Local Control of the Surgical Bed

  Up to 6 months post radiation

• Time to CNS Failure in These Patients

  Up to 5 years post radiation

• Change in Quality-of-life at 6 Months

  Up to 6 months post randomization

Study Arms (2)

Arm I - WBRT

ACTIVE COMPARATOR

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

Arm II - SRS

EXPERIMENTAL

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

Interventions

stereotactic radiosurgery RADIATION

Undergo RT

Arm II - SRS

whole-brain radiation therapy RADIATION

Undergo radiotherapy (RT)

Arm I - WBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.
• Tumor Staging Procedures - All standard tumor-staging procedures necessary to define baseline extra cranial disease status completed ≤42 days prior to pre-registration.
• Treatment with Gamma Knife or Radiosurgery - Able to be treated with either a gamma knife or a linear accelerator-based radiosurgery system.
• Age ≥ 18 years
• 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).
• Quality of Life (QOL) Questionnaires - Willing and able to complete QOL by themselves or with assistance
• ECOG Performance Status - ECOG Performance Status (PS) 0, 1, or 2.
• SRS Credentialed by IROC Houston Quality Assurance - The site's SRS facility is IROC Houston Quality Assurance approved.
• 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.
• Written Informed Consent - Provide written informed consent
• Mandatory Samples for Correlative Tests - Willing to provide mandatory blood and urine samples for correlative research purposes.

You may not qualify if:

• 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.
• Prior Cranial Radiation Therapy
• MRI or CT Scans - Inability to complete a MRI or CT scan with contrast of the head.
• Gadolinium Allergy - Known allergy to gadolinium.
• Cytotoxic Chemotherapy - Planned cytotoxic chemotherapy during the SRS or WBRT.
• Other Tumor Types - Primary germ cell tumor, small cell carcinoma, or lymphoma
• Leptomeningeal Metastasis - Widespread definitive leptomeningeal metastasis
• Location of Brain Metastasis - A brain metastasis that is located ≤ 5 mm of the optic chiasm or within the brainstem.
• Number of Unresected Lesions - Post-operative MRI or CT scan confirmed zero, one, two or three unresected lesions.
• Each unresected lesion must measure ≤ 3.0 cm in maximal extent on the contrasted post-operative MRI or CT brain scan.
• Note: The pre-registration, post-operative, brain scan may be used for the randomization scan if obtained ≤ 28 days prior to randomization.
• 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.
• Size of Resection Cavity - Post-operative MRI or CT scan confirms resection cavity measures \< 5.0 cm in maximal extent.
• Note: The pre-registration, post-operative brain scan may be used for the randomization scan if obtained ≤ 28 days prior to randomization.
• 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.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (37)

Mills - Peninsula Hospitals

Burlingame, California, 94010, United States

Location

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

John B Amos Cancer Center

Columbus, Georgia, 31904, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Lowell General Hospital

Lowell, Massachusetts, 01854, United States

Location

Saint Vincent Hospital/Reliant Medical Group

Worcester, Massachusetts, 01608, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Sanford Clinic North-Bemidji

Bemidji, Minnesota, 56601, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Wentworth-Douglass Hospital

Dover, New Hampshire, 03820, United States

Location

Somerset Medical Center

Somerville, New Jersey, 08876, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28233-3549, United States

Location

Sanford Bismarck Medical Center

Bismarck, North Dakota, 58501, United States

Location

Sanford Clinic North-Fargo

Fargo, North Dakota, 58102, United States

Location

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

Location

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, 44304, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, 97210, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Saint Luke's University Hospital-Bethlehem Campus

Bethlehem, Pennsylvania, 18015, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Aria Health-Torresdale Campus

Philadelphia, Pennsylvania, 19114, United States

Location

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, 57104, United States

Location

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117, United States

Location

Thompson Cancer Survival Center

Knoxville, Tennessee, 37916, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

Saint Vincent Hospital

Green Bay, Wisconsin, 54301, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (3)

• 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.

  PMID: 36472389 DERIVED

• 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.

  PMID: 36264568 DERIVED

• 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.

  PMID: 28687377 DERIVED

Related Links

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

MeSH Terms

Conditions

Neoplasm Metastasis; Neurotoxicity Syndromes; Radiation Injuries; Brain Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Wounds and Injuries; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Paul D. Brown, M.D.
• Organization: Mayo Clinic

brown.paul@mayo.edu

(713) 563-2415

Study Officials

• Paul D. Brown, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2011
• First Posted: June 14, 2011
• Study Start: July 1, 2011
• Primary Completion: August 1, 2016
• Study Completion: December 15, 2019
• Last Updated: September 16, 2022
• Results First Posted: July 26, 2018

Record last verified: 2022-09

Locations

US (37)