Cognitive/Functional Effects, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
cognitive/functional effects, tumors metastatic to brain, unspecified adult solid tumor, protocol specific
Brief summary
RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sunitinib malate works after stereotactic radiosurgery in treating patients with newly diagnosed brain metastases.
Detailed description
OBJECTIVES: Primary * Determine the CNS progression-free survival rate in patients with 1-3 newly diagnosed brain metastases treated with sunitinib malate after stereotactic radiosurgery (SRS). Secondary * Determine the rate of local (site of SRS treatment) failure at 12 months in these patients. * Determine the median time to CNS disease progression in these patients. * Determine the overall survival of these patients. * Determine the time to progression of systemic disease in these patients. * Evaluate the safety of sunitinib malate when administered after SRS in these patients. * Assess the neurocognitive effects of SRS followed by sunitinib malate in these patients. OUTLINE: Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Patients undergo neuropsychological battery testing at baseline and periodically during study to assess cognitive function (memory, verbal fluency, visual-motor speed, executive function, and motor dexterity), activities of daily living, and quality of life.
Interventions
DRUGsunitinib malate
Treatment will be administered on an outpatient basis. Patients will receive sunitinib 37.5mg once daily in the morning without regard to meals in repeated 6-week cycles comprising daily therapy for 4 weeks followed by a 2-week rest period. Patients who tolerate this dose may increase the dose to 50 mg once daily.
OTHERcognitive assessment
The memory test has six alternate forms. The other tests measure motor and information processing speed and are relatively resistant to the effects of practice. The total time for test administration, including the QOL and symptom measures, is 40 minutes.The difference between the pre-treatment baseline and follow-up assessment scores will be determined by the reliable change (RC) index. This index is derived from the standard error of measurement (SEM) for each test in the battery: 1 (deterioration), 2 (no change), or and 3 (improved).
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed carcinoma * Has 1-3 newly diagnosed brain metastases amenable to stereotactic radiosurgery * Patients may enroll up to 1 month after the completion of stereotactic radiosurgery provided they can undergo the required neuropsychiatric battery before beginning treatment. * Patients must begin treatment within 1 month of stereotactic radiosurgery. * No CNS metastases from lymphoma or small cell lung cancer * No leptomeningeal metastases * No CNS complications requiring urgent neurosurgical intervention (e.g., resection or shunt placement) PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% (RTOG RPA class I or II) * Life expectancy \> 6 weeks * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9.0 g/dL (transfusion allowed) * AST and ALT ≤ 2.5 times upper limit of normal (ULN) * Total serum bilirubin ≤ 1.5 times ULN * Serum calcium ≤ 12.0 mg/dL * Serum creatinine ≤ 2.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Willing and able to comply with schedule visits, treatment plans, laboratory tests, and other study procedures * No medical problem (unrelated to the malignancy) that would pose an undue risk or that would limit full compliance with the study * No unresolved bowel obstruction * No uncontrolled infectious process * No evidence of bleeding diathesis or coagulopathy * Hematuria from a primary renal tumor is allowed provided all other eligibility criteria are met * No hypertension that cannot be controlled by medications to a blood pressure of \< 160/90 mm Hg * None of the following within the past 6 months: * Myocardial infarction * Severe/unstable angina * Severe peripheral vascular disease (claudication) or procedure on peripheral vasculature * Coronary/peripheral artery bypass graft * NYHA class II-IV congestive heart failure * Cerebrovascular accident or transient ischemic attack * Clinically significant bleeding * Deep venous thrombosis or pulmonary embolism * No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of study results and, in the judgement of the investigator, would make the patient inappropriate for entry into this study PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior sunitinib malate * No prior cranial external beam radiotherapy * No concurrent coumadin or other agents containing warfarin, except for low-dose coumadin (≤ 1 mg) administered prophylactically for maintenance of in-dwelling lines or ports * No concurrent hepatic enzyme-inducing anticonvulsants * No concurrent participation in another clinical trial * No other concurrent investigational agents * Concurrent steroids allowed provided dose is stable for ≥ 1 week * Concurrent systemic therapy for management of stable systemic disease allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Central Nervous System (CNS) Progression-free Survival Rate | 6 months after stereotactic radiosurgery (SRS) | The number of subjects surviving at least six months from SRS without progressive disease anywhere in the brain (local or regional failure), assessed by the McDonald's standard criteria.Progressive neurologic abnormalities not explained by causes unrelated to tumor progression (e.g. anticonvulsant or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the size of the tumor by MRI/CT scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to CNS Disease Progression | up to12 months from SRS | Time to disease progression will be recorded from the first day of protocol therapy until the criteria for disease progression are met, patient death from any cause or removal of the patient from study for any reason, whichever comes first. |
| Overall Survival | 12 months from SRS | The number of subjects surviving at least 12 months from stereotactic radiosurgery. |
| Time to Progression | at 3 yrs from SRS | Time to progression (all sites of disease) - interval between stereotactic radiosurgery and the earliest date of progression (systemic or CNS) or death due to any cause. |
| Central Nervous System (CNS) Progression-free Survival Rate | 12 months after stereotactic radiosurgery (SRS) | The number of subjects surviving at least 12 months from SRS without progressive disease anywhere in the brain (local or regional failure), assessed by the McDonald's standard criteria. Progressive neurologic abnormalities not explained by causes unrelated to tumor progression (e.g. anticonvulsant or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the size of the tumor by MRI/CT scan. |
| Neurocognitive Effects | at 2 months after treatment | The number of patients that had statistically significant change (p's \> 0.05) in their neurocognitive assessment (improvement or decline) from baseline. Neurocognitive function was assessed in several domains, including memory, verbal fluency, visual-motor speed, executive function and motor dexterity.The difference between the pre-treatment baseline and follow-up assessment scores were determined by the reliable change (RC) index. RC Index: 1=deterioration, 2=no change, 3=improved |
| Safety and Tolerability | 3 years from study start | Number of patients that experienced treatment-related G 3-4 adverse events. |
| Rate of Local Failure at 12 Months | 12 months | Rate of local vs regional failure -rates of progression at site of stereotactic radiosurgery (local failure)vs progression anywhere else in CNS (regional failure). |
Countries
United States
Participant flow
Recruitment details
Fourteen patients were entered onto this trial between 8/2009 and 6/2011 from Cleveland Clinic and Henry Ford Health System.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib Malate Oral sunitinib malate (37.5mg)once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Patients undergo neuropsychological battery testing at baseline and periodically during study to assess cognitive function (memory, verbal fluency, visual-motor speed, executive function, and motor dexterity), activities of daily living, and quality of life. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Sunitinib Malate |
|---|---|
| Age, Continuous | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 7 / 14 |
Outcome results
Primary
Central Nervous System (CNS) Progression-free Survival Rate
The number of subjects surviving at least six months from SRS without progressive disease anywhere in the brain (local or regional failure), assessed by the McDonald's standard criteria.Progressive neurologic abnormalities not explained by causes unrelated to tumor progression (e.g. anticonvulsant or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the size of the tumor by MRI/CT scan.
Time frame: 6 months after stereotactic radiosurgery (SRS)
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Malate | Central Nervous System (CNS) Progression-free Survival Rate | 7 participants |
Secondary
Central Nervous System (CNS) Progression-free Survival Rate
The number of subjects surviving at least 12 months from SRS without progressive disease anywhere in the brain (local or regional failure), assessed by the McDonald's standard criteria. Progressive neurologic abnormalities not explained by causes unrelated to tumor progression (e.g. anticonvulsant or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the size of the tumor by MRI/CT scan.
Time frame: 12 months after stereotactic radiosurgery (SRS)
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Malate | Central Nervous System (CNS) Progression-free Survival Rate | 6 participants |
Secondary
Median Time to CNS Disease Progression
Time to disease progression will be recorded from the first day of protocol therapy until the criteria for disease progression are met, patient death from any cause or removal of the patient from study for any reason, whichever comes first.
Time frame: up to12 months from SRS
Population: Intent to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib Malate | Median Time to CNS Disease Progression | 6.6 months |
Secondary
Neurocognitive Effects
The number of patients that had statistically significant change (p's \> 0.05) in their neurocognitive assessment (improvement or decline) from baseline. Neurocognitive function was assessed in several domains, including memory, verbal fluency, visual-motor speed, executive function and motor dexterity.The difference between the pre-treatment baseline and follow-up assessment scores were determined by the reliable change (RC) index. RC Index: 1=deterioration, 2=no change, 3=improved
Time frame: at 2 months after treatment
Population: Due to the small number of patients accrued there was not enough data for analysis of this outcome.
Secondary
Overall Survival
The number of subjects surviving at least 12 months from stereotactic radiosurgery.
Time frame: 12 months from SRS
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Malate | Overall Survival | 7 participants |
Secondary
Rate of Local Failure at 12 Months
Rate of local vs regional failure -rates of progression at site of stereotactic radiosurgery (local failure)vs progression anywhere else in CNS (regional failure).
Time frame: 12 months
Population: Due to the small number of patients accrued there was not enough data for analysis of this outcome.
Secondary
Safety and Tolerability
Number of patients that experienced treatment-related G 3-4 adverse events.
Time frame: 3 years from study start
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Malate | Safety and Tolerability | 9 participants |
Secondary
Time to Progression
Time to progression (all sites of disease) - interval between stereotactic radiosurgery and the earliest date of progression (systemic or CNS) or death due to any cause.
Time frame: at 3 yrs from SRS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib Malate | Time to Progression | 4.8 months |