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

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

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.

Study Overview

• Status: Terminated
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Metastatic Cancer; Cognitive/Functional Effects
• Intervention / Treatment: Drug: sunitinib malate; Other: cognitive assessment

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sunitinib malate; 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.

Drug: sunitinib 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.; Other Names: Sutent; SUNITINIB L-Malate salt; SU010398; PHA-290940AD; SUNITINIB; Other: cognitive 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).; Other Names: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months after stereotactic radiosurgery (SRS)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months after stereotactic radiosurgery (SRS)
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.	up to12 months from SRS
Overall Survival	The number of subjects surviving at least 12 months from stereotactic radiosurgery.	12 months from SRS
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.	at 3 yrs from SRS
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).	12 months
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	at 2 months after treatment
Safety and Tolerability	Number of patients that experienced treatment-related G 3-4 adverse events.	3 years from study start

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David M. Peereboom, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: May 28, 2009
• First Submitted That Met QC Criteria: May 28, 2009
• First Posted (Estimate): May 29, 2009

Study Record Updates

• Last Update Posted (Estimate): September 29, 2014
• Last Update Submitted That Met QC Criteria: September 25, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; tumors metastatic to brain; cognitive/functional effects
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: CASE1308 (Other Identifier: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No