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A Phase III Trial of Post-Surgical Stereotactic Radiosurgery (SRS) Compared With Whole Brain Radiotherapy (WBRT) for Resected Metastatic Brain Disease


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Cognitive/Functional Effects, Metastatic Cancer, Neurotoxicity, Radiation Toxicity, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase III Trial of Post-Surgical Stereotactic Radiosurgery (SRS) Compared With Whole Brain Radiotherapy (WBRT) for Resected Metastatic Brain Disease


OBJECTIVES:

Primary

- To ascertain in patients with one to four brain metastases whether there is improved
overall survival in patients who receive stereotactic radiosurgery (SRS) to the
surgical bed compared to patients who receive whole-brain radiotherapy (WBRT).

- To ascertain in patients with one to four brain metastases whether there is less
neurocognitive progression at 6 months post-radiation in patients who receive SRS to
the surgical bed compared to patients who receive WBRT.

Secondary

- To ascertain in patients with resected brain metastases whether there is improved
quality-of-life (QOL) in patients who receive SRS to the surgical bed compared to
patients who receive WBRT.

- To ascertain in patients with one to four brain metastases whether there is equal
longer time to central nervous system (CNS) failure (brain) in patients who receive SRS
to the surgical bed compared to patients who receive WBRT.

- To ascertain 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.

- To ascertain 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.

- To tabulate and descriptively compare the post-treatment adverse events associated with
the interventions.

- To evaluate local tumor bed recurrence at 6 months with post-surgical SRS to the
surgical bed in comparison to WBRT.

- To evaluate time to local recurrence with post-surgical SRS to the surgical bed in
comparison to WBRT.

- 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.

Exploratory

- To evaluate radiation changes in the limbic system that may correlate with
neurotoxicity using brain MRI scans.

- To determine whether Apo E (i.e., Apo E2, Apo E3, and Apo E4) genotyping may prove to
be a predictor of radiation-induced neurocognitive decline (or neuroprotection).

- To determine whether inflammatory markers (i.e., IL-1, IL-6, and TNF-α) may prove to be
predictors of radiation-induced neurocognitive decline.

- To determine whether oxidative stress biomarkers (i.e., protein carbonyl content, lipid
hydroperoxides, and isoprostane levels) may prove to be predictors of radiation-induced
neurocognitive decline.

- To determine whether hormone and growth factors [i.e., glucocorticoids (e.g.,
cortisol), gonadal steroids (e.g., estradiol, testosterone, progesterone), growth
hormone, human chorionic gonadotropin (hCG), insulin-like growth factor-1 (IGF-1), and
neuronal growth factor (NGF)] may prove to be a predictor of radiation-induced
neurocognitive decline.

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). 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.

Serum, whole blood, and urine samples are collected at baseline and periodically during
study for genetic markers, inflammatory markers, oxidative stress biomarkers, and hormone
and growth factor studies by ELISA and other assays.

Patients complete the Functional Assessment of Cancer Therapy-Brain (FACT-BR), the
activities of daily living (ADLs), the Fatigue/Uniscale Assessment, and the Linear Analog
Self Assessment (LASA) quality-of-life questionnaires at baseline and periodically during
study. Neurocognitive functions, such as memory, verbal fluency, visual attention, executive
function, and delayed memory, are also assessed.

After completion of study therapy, patients are followed up periodically for 5 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Four or fewer brain metastases (as defined on the pre-operative MRI brain scan) and
status post resection of one of the lesions

- Pathology from the resected brain metastasis must be consistent with a non-central
nervous system primary site

- 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

- Any unresected lesions must measure ≤ 3.0 cm in maximal extent on the contrasted MRI
brain scan obtained ≤ 35 days prior to pre-registration

- The metastases size restriction does not apply to the resected brain metastasis;
with resected brain metastases only surgical cavity size determines eligibility

- Post-operative MRI 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 brain scan

- 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

- 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

- The pre-registration, post-operative brain scan may be used for the planning
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

- 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

- All standard tumor-staging procedures necessary to define baseline extracranial
disease status completed ≤ 42 days prior to pre-registration

- No primary germ cell tumor, small cell carcinoma, or lymphoma

- No widespread definitive leptomeningeal metastasis

- No brain metastasis that is located ≤ 5 mm of the optic chiasm or within the
brainstem

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0, 1, or 2

- Ability to be treated with either a gamma knife or a linear accelerator-based
radiosurgery system

- Willing and able to complete neurocognitive examination without assistance

- Willing and able to complete quality-of-life (QOL) questionnaires by themselves or
with assistance

- Willing to provide mandatory blood and urine samples for correlative research
purposes

- None of the following:

- Pregnant or nursing

- Men or women of childbearing potential who are unwilling to employ adequate
contraception through out the study and for men for up to 3 months after
completing treatment

- Able to complete a MRI with contrast of the head

- No known allergy to gadolinium

PRIOR CONCURRENT THERAPY:

- No prior cranial radiotherapy

- No planned cytotoxic chemotherapy during the stereotactic radiosurgery (SRS) or
whole-brain radiotherapy (WBRT)

- Concurrent hormonal agents, steroids, and/or anticonvulsants allowed

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Neurocognitive progression at 6 months post-radiation in patients who received SRS compared to patients who received WBRT

Safety Issue:

No

Principal Investigator

Paul D. Brown, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

Unspecified

Study ID:

CDR0000701474

NCT ID:

NCT01372774

Start Date:

July 2011

Completion Date:

Related Keywords:

  • Cognitive/Functional Effects
  • Metastatic Cancer
  • Neurotoxicity
  • Radiation Toxicity
  • Unspecified Adult Solid Tumor, Protocol Specific
  • neurotoxicity
  • radiation toxicity
  • cognitive/functional effects
  • tumors metastatic to brain
  • unspecified adult solid tumor, protocol specific
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Neurotoxicity Syndromes
  • Radiation Injuries

Name

Location

Mayo Clinic Cancer CenterRochester, Minnesota  55905
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Mount Sinai Medical CenterMiami Beach, Florida  33140
Swedish Medical CenterEnglewood, Colorado  80110
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
United HospitalSt. Paul, Minnesota  55102
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Rapid City Regional HospitalRapid City, South Dakota  57709
Memorial Hospital of South BendSouth Bend, Indiana  46601
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
USC/Norris Comprehensive Cancer Center and HospitalLos Angeles, California  90033-0804
Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical CenterMilwaukee, Wisconsin  53201-2901
Thompson Cancer Survival CenterKnoxville, Tennessee  37916
Advocate Christ Medical CenterOak Lawn, Illinois  60453
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
M.D. Anderson Cancer Center at OrlandoOrlando, Florida  32806
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
Rosenfeld Cancer Center at Abington Memorial HospitalAbington, Pennsylvania  19001
Morgan Cancer Center at Lehigh Valley Hospital - Cedar CrestAllentown, Pennsylvania  18105
Mercy Regional Cancer Center at Mercy Medical CenterCedar Rapids, Iowa  52403
CentraCare Clinic - River CampusSt. Cloud, Minnesota  56303
Billings Clinic - DowntownBillings, Montana  59107-7000
Summa Center for Cancer Care at Akron City HospitalAkron, Ohio  44309-2090
Mount Carmel St. Ann's Cancer CenterWesterville, Ohio  43081
Legacy Good Samaritan Hospital & Comprehensive Cancer CenterPortland, Oregon  97210
Salem Hospital Regional Cancer Care ServicesSalem, Oregon  97309-5014
Saint Joseph's HospitalMarshfield, Wisconsin  54449
Mid Dakota Clinic, PCBismarck, North Dakota  58501
Louisville Oncology at Norton Cancer Institute - LouisvilleLouisville, Kentucky  40202
Medcenter One Hospital Cancer Care CenterBismarck, North Dakota  58501
Cancer Institute of Cape Girardeau, LLCCape Girardeau, Missouri  63703
Frankford Hospital Cancer Center - Torresdale CampusPhiladelphia, Pennsylvania  19114
Tufts Medical Center Cancer CenterBoston, Massachusetts  02111
Seacoast Cancer Center at Wentworth - Douglass HospitalDover, New Hampshire  03820