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

Primary Purpose

Cognitive/Functional Effects, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

sunitinib malate

cognitive assessment

About this trial

This is an interventional treatment trial for Cognitive/Functional Effects focused on measuring cognitive/functional effects, tumors metastatic to brain, unspecified adult solid tumor, protocol specific

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Henry Ford Health System
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sunitinib malate

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Overall Survival

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

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.

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).

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

Safety and Tolerability

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

Full Information

NCT ID

NCT00910039

First Posted

May 28, 2009

Last Updated

September 25, 2014

Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00910039

Brief Title

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

Official Title

SUNDANCE Trial: Phase II Trial of Sunitinib as Maintenance Therapy After Stereotactic Radiosurgery in Patients With 1-3 Newly Diagnosed Brain Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

September 2014

Overall Recruitment Status

Terminated

Why Stopped

Slow Accrual

Study Start Date

April 2009 (undefined)

Primary Completion Date

January 2012 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cognitive/Functional Effects, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Keywords

cognitive/functional effects, tumors metastatic to brain, unspecified adult solid tumor, protocol specific

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sunitinib malate

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

sunitinib malate

Other Intervention Name(s)

SUNITINIB L-Malate salt, SU010398; PHA-290940AD, Sutent, SUNITINIB

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

cognitive assessment

Other Intervention Name(s)

Cognitive Function Tests:, Memory Hopkins Verbal Learning Test, Verbal fluency Controlled Oral Word Association, Visual-motor speed Trail Making Test Part A, Executive Function Trail Making Test Part B, Motor dexterity Grooved Pegboard 3, Function Test:, Quality of life (QOL) was evaluated with a self-report measure (FACT-BRREF).

Intervention Description

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).

Primary Outcome Measure Information:

Title

Central Nervous System (CNS) Progression-free Survival Rate

Description

Time Frame

6 months after stereotactic radiosurgery (SRS)

Secondary Outcome Measure Information:

Title

Central Nervous System (CNS) Progression-free Survival Rate

Description

Time Frame

12 months after stereotactic radiosurgery (SRS)

Title

Median Time to CNS Disease Progression

Description

Time Frame

up to12 months from SRS

Title

Overall Survival

Description

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

Time Frame

12 months from SRS

Title

Time to Progression

Description

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

Title

Rate of Local Failure at 12 Months

Description

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

Title

Neurocognitive Effects

Description

Time Frame

at 2 months after treatment

Title

Safety and Tolerability

Description

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

Time Frame

3 years from study start

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David M. Peereboom, MD

Organizational Affiliation

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Henry Ford Health System

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Name

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

12. IPD Sharing Statement

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

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