- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00928226
Study of Fractionated Stereotactic Radiosurgery to Treat Large Brain Metastases
A Phase I/II Study of Fractionated Stereotactic Radiosurgery to Treat Large Brain Metastases
The maximum tolerated dose of 3-session (ie, treatment) stereotactic radiosurgery (SRS) to treat brain metastases greater than 4.2 cm³ in size will be determined.
This study investigates if increasing radiation dose improves outcome for patients without greater toxicity (side effects).
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Brain metastases are the most common intracranial tumors and occur in approximately 25% of patients with cancer. In the US, approximately 170,000 cancer patients a year are diagnosed with brain metastases.
The prognosis of patients with brain metastases is variable and depends on several factors, including performance status, age, control of the primary tumor, and extent of extracranial disease. Historically, patients with brain metastases who receive supportive care only have median survival of 1 to 2 months. However, a subgroup of patients with favorable prognosis who undergo treatment can enjoy an extended life expectancy with median survival of 10 to 16 months. Treatment options for brain metastases include medical management, surgery, and radiation therapy (radiotherapy). Both surgery and radiotherapy have an important role in management of brain metastases, and an optimized treatment plan may include both. It is well-established that surgery followed by conventional whole brain radiation (WBRT) decreases local recurrence and improves median survival compared to WBRT alone. Conventional WBRT is administered as radiotherapy to the whole cranium delivered in 10 to 20 daily treatments.
For this study, radiotherapy will be delivered using stereotactic radiosurgery (SRS) to treat individual metastases. SRS has the advantage of sparing normal brain tissue. In SRS, high energy radiation is precisely directed at the target lesion. Due to the steep fall-off of the radiation dose away from the target, the advantage of relative sparing of the normal brain may be realized. The present study is based on a rationale of treating brain metastases with surgical resection followed by adjuvant SRS to the resection cavity, while deferring conventional WBRT for salvage therapy.
WBRT is associated with a short-term decline in quality of life and long-term deficits in neurocognitive function ("late effects"). Late toxicity of WBRT, such as memory impairment and dementia, is usually irreversible and is likely due to demyelination, vascular damage, and necrosis. Following WBRT, the actuarial rate of neurocognitive toxicity at 2 years can be up to 49%. Recipients of WBRT may demonstrate a > 2 standard deviation decline in their performance at 6 months. Compared to SRS alone, WBRT was reported to be associated with a marked decline in learning and memory function at 4 months (49% vs 23%, in favor of SRS).
To minimize the potential late effects of WBRT, investigators have explored the use of SRS alone, deferring the use of WBRT for salvage treatment if needed. Both retrospective analyses and a prospective randomized trial reported no apparent survival benefit to combining WBRT with SRS compared to SRS alone
Primary Objectives: Determine the maximum tolerated dose (MTD) of stereotactic radiosurgery (SRS).
Secondary Objectives:
- Determine the local control rate as assessed on MRI and clinical exam.
- Determine short- and long-term adverse effects.
- Determine the distant intra-cranial control rate.
- Determine the overall survival rate.
- Assess the patient's health related quality of life.
Treatment Group assignment will be by SRS dose level. SRS will be administered as 3 fractions. Radiation dose is administered as "Greys" (or "Grays"; abbreviated Gy), a unit by which radiation is measured. Treatment Groups are as follows: Group 1 = 24 Gy (administered as 8 Gy x 3) Group 2 = 7 Gy (9 Gy x 3); Group 3 = 30 Gy (10 Gy x 3); Group 4 = 33 Gy (11 Gy x 3).
Within each Treatment Group, analysis may be stratified by tumor size and suitability for surgical resection, as below. For those participants eligible for surgical resection, the procedure will be conducted in advance of the SRS treatment.
- Strata A will be those with tumors 4.2 to 14.1 cm³, and suitable for resection.
- Strata B will be those with tumors 4.2 to 14.1 cm³, but not suitable for resection.
- Strata C will be those with tumors 14.2 to 33.5 cm³, and suitable for resection.
- Strata D will be those with tumors 14.2 to 33.5 cm³, but not suitable for resection.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
California
-
Stanford, California, United States, 94305
- Stanford University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
INCLUSION CRITERIA
- Age 18 years and older
- Pathologically-proven solid tumor malignancy
- 1 to 4 brain metastases, one of which is 4.2 to 33.5 cm³.
- Prior surgery or SRS is allowed as long as the target metastatic lesion in this study has not previously been treated with SRS.
- Prior cytotoxic systemic therapy must be completed ≥ 5 days prior to radiosurgery. No concurrent cytotoxic systemic therapy along with SRS. Cytotoxic systemic therapy to start ≥ 5 days after the completion of SRS.
- Life expectancy of ≥ 12 weeks.
- Ability to understand and the willingness to sign a written informed consent.
EXCLUSION CRITERIA
- Previously treated with whole brain irradiation
- Target metastatic lesion previously been treated with SRS.
- > 4 total brain metastases at the time of initial evaluation.
- Pregnant
- Unable to give informed consent.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1 - 24 Grey SRS
24 Grey administered as 8 Gy x 3 fractions
|
Standard of care
Other Names:
Standard of care
|
Experimental: Arm 2 - 27 Grey SRS
27 Grey administered as 9 Gy x 3 fractions
|
Standard of care
Other Names:
Standard of care
|
Experimental: Arm 3 - 30 Grey SRS
30 Grey administered as 10 Gy x 3 fractions
|
Standard of care
Other Names:
Standard of care
|
Experimental: Arm 4 - 33 Grey SRS
33 Grey administered as 11 Gy x 3 fractions
|
Standard of care
Other Names:
Standard of care
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD)
Time Frame: 60 days
|
The maximum-tolerated Dose (MTD) of stereotactic radiosurgery (SRS) was assessed based on the number of dose-limiting toxicities (DLTs). DLT was defined as any treatment-related grade 3, 4, or 5 central nervous system (CNS) radiation morbidity observed within 30 days of radiosurgery. CNS radiation morbidity was further defined as.
The outcome is expressed as number of DLTs experienced by participants, by radiotherapy dose cohort and tumor size, a number without dispersion. Per protocol, the MTD of SRS was defined as either the dose level below that at which 4+ DLTs were experienced by 12 subjects, or the maximum dose administered without MTD. |
60 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Local Disease Control
Time Frame: 12 months
|
Local disease control (treatment response) was assessed on the basis of tumor size before and 12 months after treatment. Treatment response was based on the following criteria. Tumor area is determined as the product of 2 measurements of lesion diameter.
Local control is defined as as any treatment response other than progression. The outcome is as the number of participants that did not progress, by radiotherapy dose cohort and tumor size, a number without dispersion. |
12 months
|
Distant Intra-cranial Disease Control
Time Frame: 12 months
|
Distant treatment failure (failure to achieve or maintain disease control) is defined as the radiographic appearance of a new or enhancing lesion more than 5 mm from the radiosurgical target volume.
The outcome is expressed as the number of participants who have distant treatment failure after radiotherapy dose cohort and tumor size, a number without dispersion.
|
12 months
|
Adverse Effects Within 30 Days
Time Frame: 30 days
|
Short-term adverse effects are defined as any adverse event related to the stereotactic radiosurgery (SRS), and occurring within 30 days of SRS.
The outcome is expressed as the number of events experienced by participants, by radiotherapy dose cohort and tumor size, a number without dispersion.
|
30 days
|
Adverse Effects More Than 30 Days up to 1 Year
Time Frame: after 30 days and up to 1 year
|
Long-term adverse effects are defined as any adverse event related to the stereotactic radiosurgery (SRS), and occurring more 30 days but within 12 months of SRS.
The outcome is expressed as the number of events experienced by participants, by radiotherapy dose cohort and tumor size, a number without dispersion.
|
after 30 days and up to 1 year
|
Overall Survival (OS)
Time Frame: 3 years
|
Overall survival (OS) is assessed as remaining alive 3 years after stereotactic radiosurgery (SRS) therapy.
The outcome is expressed as the number of participants alive 3 years after SRS, by radiotherapy dose cohort and tumor size, a number without dispersion.
|
3 years
|
Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30
Time Frame: 6 months
|
Health-related quality of life (HR-QoL), was assessed based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients (QLQ-C30) survey, a survey of 28 questions with the following responses / numerical values.
|
6 months
|
Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20
Time Frame: 6 months
|
Health-related quality of life (HR-QoL), was assessed based on the European Organisation for Research and Treatment of Cancer (EORTC) Brain Cancer Module (QLQ-BN20), a survey of 20 questions with the following responses / numerical values.
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Clara Choi, Stanford University
- Principal Investigator: Scott Soltys, Stanford University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB-15107
- SU-04272009-2418 (Other Identifier: Stanford University)
- BRN0010 (Other Identifier: OnCore)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neoplasm Metastasis
-
Betta Pharmaceuticals Co., Ltd.Recruiting
-
BayerCompleted
-
BayerCompletedNeoplasm Metastasis / Bone and BonesBelgium, Spain, Taiwan, United States, Japan, Russian Federation, Canada, Finland, Korea, Republic of, Singapore, Australia, Germany, Israel, United Kingdom, Italy, France, Poland, Brazil, Czechia, Norway, Sweden, Hong Kong
-
National Cancer Institute (NCI)TerminatedCancer | Neoplasm Metastasis | Metastasis | Neoplasm | Radiation OncologyUnited States
-
Cho Ray HospitalUniversity of Medicine and Pharmacy at Ho Chi Minh CityRecruitingSynchronous Neoplasm | Liver Metastasis Colon CancerVietnam
-
MedtronicNeuroCompletedMetastasis Spine | Metastasis to BoneUnited States, Luxembourg, Germany, France, Canada
-
Li MinRecruiting
-
Da FuGanzhou City People's HospitalRecruiting
-
University of Mississippi Medical CenterCompletedMetastasisUnited States
-
Assiut UniversityNot yet recruiting
Clinical Trials on Fractionated Stereotactic Radiosurgery (SRS)
-
Steven BurtonActive, not recruiting
-
University of Michigan Rogel Cancer CenterCompleted
-
Medical College of WisconsinRecruitingBrain MetastasesUnited States
-
Duke UniversityVarian Medical SystemsCompleted
-
University of Texas Southwestern Medical CenterRecruitingBrain Neoplasms, Adult, MalignantUnited States
-
University of UtahRecruiting
-
Northwell HealthCompletedCancer of the OropharynxUnited States
-
Juergen DebusHeidelberg UniversityCompletedAdult Solid Tumor | Brain MetastasesGermany
-
Dr David MathieuCentre de recherche du Centre hospitalier universitaire de Sherbrooke; Université...Recruiting