Stereotactic Radiosurgery Compared to Observation in Treating Patients With Brain Metastases

• ClinicalTrials.gov Identifier: NCT00950001
• Recruitment Status: Active, not recruiting
• First Posted: July 31, 2009
• Last Update Posted: February 20, 2024
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Tracking Information

• First Submitted Date: July 30, 2009
• First Posted Date: July 31, 2009
• Last Update Posted Date: February 20, 2024
• Actual Study Start Date: August 13, 2009
• Estimated Primary Completion Date: April 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 29, 2019)

Time to local recurrence [ Time Frame: 6 months ]

A univariate test between groups will be conducted using a log rank test of Kaplan-Meier survival estimates and multivariate analyses will be conducted via the Cox proportional hazards model. The hazard ratio comparing each arm will be computed for each endpoint with and without adjustment for other covariates. Confidence intervals (95%) will be computed for the hazard ratio estimates. The proportion of patients experiencing neurological complications will be computed via univariate and multivariate logistic regression analysis.

• Original Primary Outcome Measures (submitted: July 30, 2009): Time to Local Recurrence (TTLR) [ Time Frame: Differences in TTLR will be monitored at 3 timepoints and will take place: 1) after a total of 39 events occur; 2) after 77 events occur; and 3) after at least 115 events occur. ]

Current Secondary Outcome Measures (submitted: May 29, 2019)

• Overall survival [ Time Frame: Up to 8 years ]
  A univariate test between groups will be conducted using a log rank test of Kaplan-Meier survival estimates and multivariate analyses will be conducted via the Cox proportional hazards model. The hazard ratio comparing each arm will be computed for each endpoint with and without adjustment for other covariates. Confidence intervals (95%) will be computed for the hazard ratio estimates.
• Development of distant brain metastases [ Time Frame: Up to 8 years ]
  A univariate test between groups will be conducted using a log rank test of Kaplan-Meier survival estimates and multivariate analyses will be conducted via the Cox proportional hazards model. The hazard ratio comparing each arm will be computed for each endpoint with and without adjustment for other covariates. Confidence intervals (95%) will be computed for the hazard ratio estimates.
• Incidence of complications related to treatment [ Time Frame: Up to 8 years ]
  The proportions of patients experiencing neurological complications will be computed via univariate and multivariate logistic regression analysis. The proportion of complications resulting in prolongation of hospital stay will also be computed. The odds ratios comparing both arms will be computed with and without adjustment for other covariates. Confidence intervals (95%) will be computed for the odds ratio estimates.
• Proportion of patients experiencing neurological complications [ Time Frame: Up to 8 years ]
  Computed via univariate and multivariate logistic regression analysis.
• Proportion of complications resulting in prolongation of hospital stay [ Time Frame: Up to 8 years ]
  Will be computed.
• Time to first neurological complication [ Time Frame: Up to 8 years ]
  A univariate test between groups will be conducted using a log rank test of Kaplan-Meier survival estimates and multivariate analyses will be conducted via the Cox proportional hazards model. The hazard ratio comparing each arm will be computed for each endpoint with and without adjustment for other covariates. Confidence intervals (95%) will be computed for the hazard ratio estimates.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Stereotactic Radiosurgery Compared to Observation in Treating Patients With Brain Metastases
• Official Title: Efficacy of Post-Surgical Stereotactic Radiosurgery for Metastatic Brain Disease: A Randomized Trial
• Brief Summary: This randomized phase III trial studies stereotactic radiosurgery to see how well it works compared to clinical observation after surgery in treating patients with brain metastases. Stereotactic radiosurgery, a type of radiation therapy, may be able to send x-rays directly to the tumor and cause less damage to normal tissue.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate benefit of post-surgical stereotactic radiosurgery (SRS) on the resection bed in providing 6 month local control (decreasing the risk of local tumor recurrence) when compared to surgical resection alone.

SECONDARY OBJECTIVES:

I. Overall survival, development of distant brain metastases and complications related to treatment.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo stereotactic radiosurgery to the surgical cavity within 30 days of the craniotomy.

ARM II: Patients undergo clinical observation after craniotomy.

After completion of study treatment, patients are followed up at 5-8 weeks, every 6-9 weeks for 1 year, every 3-4 months for 1 year, and then every 6 months thereafter.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Malignant Neoplasm in the Brain

Intervention

Radiation: Stereotactic Radiosurgery

Undergo SRS

Other Names:

• Stereotactic External Beam Irradiation
• stereotactic external-beam radiation therapy
• stereotactic radiation therapy
• Stereotactic Radiotherapy
• stereotaxic radiation therapy
• stereotaxic radiosurgery

Study Arms

• Experimental: Arm I (SRS)
  Patients undergo stereotactic radiosurgery to the surgical cavity within 30 days of the craniotomy.
  Intervention: Radiation: Stereotactic Radiosurgery
• No Intervention: Arm II (observation)
  Patients undergo clinical observation after craniotomy.

• Publications *: Mahajan A, Ahmed S, McAleer MF, Weinberg JS, Li J, Brown P, Settle S, Prabhu SS, Lang FF, Levine N, McGovern S, Sulman E, McCutcheon IE, Azeem S, Cahill D, Tatsui C, Heimberger AB, Ferguson S, Ghia A, Demonte F, Raza S, Guha-Thakurta N, Yang J, Sawaya R, Hess KR, Rao G. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1040-1048. doi: 10.1016/S1470-2045(17)30414-X. Epub 2017 Jul 4. Erratum In: Lancet Oncol. 2017 Aug;18(8):e433. Lancet Oncol. 2017 Sep;18(9):e510.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 30, 2009): 132
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2025
• Estimated Primary Completion Date: April 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients must be older than 3 years of age (radiosurgical frames cannot be placed on children younger than age 3).
2. Patients must have 3 or fewer newly diagnosed metastatic lesions in the brain with a complete resection of at least one lesion as determined the study neuroradiologist.
3. The resection cavity must have a maximum diameter of less than or equal to 4cm. This criteria will be determined by the study radiologist.
4. Additional unresected brain metastases (up to 2) must have a maximum diameter of less than or equal to 3 cm.
5. Patients must be considered candidates for SRS within 30 days of surgical resection.
6. Patients must have a Karnofsky Performance Scores (KPS) of at least 70 at the first post operative visit. Patients under 18 years of age must have a Lansky Performance Score of of at least 70.
7. Patients must be able to undergo an MRI scan.
8. Patients must agree to randomization as documented by signing the Institutional Review Board (IRB) approved consent form.

Exclusion Criteria:

1. Patients who have received prior radiation therapy to the brain for any reason.
2. There is radiographic evidence of leptomeningeal disease prior to study entry.
3. The primary tumor is small-cell lung cancer, lymphoma, leukemia, or multiple myeloma.
4. For females, if they are pregnant or breast-feeding (The exclusion is made because gadolinium may be teratogenic in pregnancy).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00950001
• Other Study ID Numbers: 2009-0381; NCI-2011-00542 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2009-0381 ( Other Identifier: M D Anderson Cancer Center ); P30CA016672 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: M.D. Anderson Cancer Center
• Original Responsible Party: Anita Mahajan, MD / Associate Professor, UT MD Anderson Cancer Center
• Current Study Sponsor: M.D. Anderson Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Debra NAna Yeboa; M.D. Anderson Cancer Center

• PRS Account: M.D. Anderson Cancer Center
• Verification Date: February 2024