Trial Outcomes & Findings for Sunitinib Malate After Stereotactic Radiosurgery in Treating Patients With Newly Diagnosed Brain Metastases (NCT NCT00910039)

Last Updated: 2014-09-29

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

6 months after stereotactic radiosurgery (SRS)

Results posted on

2014-09-29

Participant Flow

Fourteen patients were entered onto this trial between 8/2009 and 6/2011 from Cleveland Clinic and Henry Ford Health System.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	14
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Physician Decision	1

Baseline Characteristics

Sunitinib Malate After Stereotactic Radiosurgery in Treating Patients With Newly Diagnosed Brain Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sunitinib Malate n=14 Participants 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.
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months after stereotactic radiosurgery (SRS)

Population: Intent to treat

Outcome measures

Outcome measures
Measure	Sunitinib Malate n=14 Participants 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.
Central Nervous System (CNS) Progression-free Survival Rate	7 participants Interval 37.0 to 63.0

SECONDARY outcome

Timeframe: 12 months after stereotactic radiosurgery (SRS)

Population: Intent to treat

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.

Outcome measures

Outcome measures
Measure	Sunitinib Malate n=14 Participants 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.
Central Nervous System (CNS) Progression-free Survival Rate	6 participants

SECONDARY outcome

Timeframe: up to12 months from SRS

Population: Intent to treat

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.

Outcome measures

Outcome measures
Measure	Sunitinib Malate n=14 Participants 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.
Median Time to CNS Disease Progression	6.6 months Interval 1.5 to 19.0

SECONDARY outcome

Timeframe: 12 months from SRS

Population: Intent to treat

The number of subjects surviving at least 12 months from stereotactic radiosurgery.

Outcome measures

Outcome measures
Measure	Sunitinib Malate n=14 Participants 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.
Overall Survival	7 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sunitinib Malate n=14 Participants 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.
Time to Progression	4.8 months Interval 1.5 to 18.8

SECONDARY outcome

Timeframe: 12 months

Population: Due to the small number of patients accrued there was not enough data for analysis of this outcome.

Rate of local vs regional failure -rates of progression at site of stereotactic radiosurgery (local failure)vs progression anywhere else in CNS (regional failure).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 2 months after treatment

Population: Due to the small number of patients accrued there was not enough data for analysis of this outcome.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 years from study start

Number of patients that experienced treatment-related G 3-4 adverse events.

Outcome measures

Outcome measures
Measure	Sunitinib Malate n=14 Participants 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.
Safety and Tolerability	9 participants

Adverse Events

Sunitinib Malate

Serious events: 7 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sunitinib Malate n=14 participants at risk 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.
Blood and lymphatic system disorders Lymphopenia	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Cardiac disorders Cardiac troponin T (cTnT)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Gastrointestinal disorders Diarrhea	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Gastrointestinal disorders Vomiting	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Hemorrhage, CNS	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Aphasia	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Pain - Head/headache	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Vascular disorders Pulmonary Embolism	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.

Other adverse events

Other adverse events
Measure	Sunitinib Malate n=14 participants at risk 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.
Immune system disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	21.4% 3/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Ear and labyrinth disorders Hearing: patients without baseline audiogram and not enrolled in a monitoring program	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Blood and lymphatic system disorders Anemia	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Blood and lymphatic system disorders Leukocytes (total WBC)	28.6% 4/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Blood and lymphatic system disorders Lymphopenia	35.7% 5/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	21.4% 3/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Blood and lymphatic system disorders Platelets	50.0% 7/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Cardiac disorders Supraventricular and nodal arrhythmia - Sinus tachycardia	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Vascular disorders Hypertension	42.9% 6/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Vascular disorders Hypotension	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Investigations INR (International Normalized Ratio of prothrombin time)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Lightheadedness	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
General disorders Fatigue (asthenia, lethargy, malaise)	100.0% 14/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Psychiatric disorders Insomnia	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
General disorders Rigors/chills	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Investigations Weight gain	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Investigations Weight loss	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Skin and subcutaneous tissue disorders Bruising (in absence of Grade 3 or 4 thrombocytopenia)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Skin and subcutaneous tissue disorders Icteric Skin (Jaundice)	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (NOS)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Skin and subcutaneous tissue disorders Dry skin	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Skin and subcutaneous tissue disorders Nail changes	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Skin and subcutaneous tissue disorders Rash: hand-foot skin reaction	42.9% 6/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Endocrine disorders Thyroid function, low (hypothyroidism)	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Metabolism and nutrition disorders Anorexia	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Gastrointestinal disorders Constipation	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Gastrointestinal disorders Diarrhea	71.4% 10/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Gastrointestinal disorders Heartburn/dyspepsia	21.4% 3/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Gastrointestinal disorders Mucositis/stomatitis (functional/symptomatic) - Oral cavity	50.0% 7/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Gastrointestinal disorders Nausea	42.9% 6/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Gastrointestinal disorders Taste alteration (dysgeusia)	42.9% 6/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Respiratory, thoracic and mediastinal disorders Hemorrhage, pulmonary/upper respiratory - Lung	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Respiratory, thoracic and mediastinal disorders Hemorrhage, pulmonary/upper respiratory - Nose	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Eye disorders Sub-conjunctival hemorrhage	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Infections and infestations Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Ear and labyrinth disorders Infection with normal ANC or Grade 1 or 2 neutrophils - External ear (otitis externa)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
General disorders Edema: limb	28.6% 4/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Investigations AST, SGOT(serum glutamic oxaloacetic transaminase)	35.7% 5/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Investigations Albumin, serum-low (hypoalbuminemia)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Investigations Calcium, serum-high (hypercalcemia)	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Investigations Creatinine	28.6% 4/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Metabolism and nutrition disorders Glucose, serum-low (hypoglycemia)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Metabolism and nutrition disorders Proteinuria	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Musculoskeletal and connective tissue disorders Extremity-lower (gait/walking)	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-lower	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Confusion	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Dizziness	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Mood alteration - Agitation	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Mood alteration - Anxiety	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Mood alteration - Depression	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Neurology - Other (Right-sided Facial Drooping)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Neurology - Other (Shaking, right leg and arm)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Neuropathy: sensory	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Seizure	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Speech impairment (Slurred Speech)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Syncope (fainting)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Eye twitching	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Eye disorders Vision-blurred vision	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Eye disorders Watery eye (epiphora, tearing)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Gastrointestinal disorders Pain - Abdominal cramps	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Musculoskeletal and connective tissue disorders Pain - Back	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Musculoskeletal and connective tissue disorders Pain - Chest/thorax NOS	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Musculoskeletal and connective tissue disorders Pain - External ear	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Musculoskeletal and connective tissue disorders Pain - Extremity-limb	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Nervous system disorders Pain - Head/headache	35.7% 5/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Musculoskeletal and connective tissue disorders Pain - Joint	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Musculoskeletal and connective tissue disorders Pain - Jaw	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Musculoskeletal and connective tissue disorders Pain - Other (left groin pain)	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Respiratory, thoracic and mediastinal disorders Cough	21.4% 3/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	14.3% 2/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Renal and urinary disorders Obstruction, GU - Ureter	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Renal and urinary disorders Obstruction, GU - Urethra	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Renal and urinary disorders Renal failure	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.
Vascular disorders Thrombosis/thrombus/embolism	7.1% 1/14 • Adverse event data was collected from on study date to off study for a period of about 2.5 years.

Additional Information

David Peereboom, MD

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Phone: 216-445-6068

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place