Sunitinib in Treating Patients With Brain Metastases Caused by Kidney Cancer or Melanoma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00462982
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 17.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

RATIONALE: Sunitinib 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 works in treating patients with brain metastases caused by kidney cancer or melanoma.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer; Melanoma (Skin); Metastatic Cancer	Drug: sunitinib malate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of sunitinib malate, in terms of objective radiographic response of brain lesions, in patients with brain metastases secondary to renal cell carcinoma or melanoma.

Secondary

• Determine overall and progression-free survival.

OUTLINE: Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of SU11248 (Sunitinib) in Patients With Renal Cell Carcinoma and Melanoma Metastatic to the Brain
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sunitinib Patients will be treated with 50 mg daily for four out of every six weeks.	Drug: sunitinib malate

Outcome Measures

Primary Outcome Measures

1. Central Nervous System (CNS) Response Rate by RECIST Criteria [up to a year]

   Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques (CT, MRI, X-ray) or as >10 mm with spiral CT scan. This study will use a minimum diameter of 10 mm for measurable lesions in the brain, regardless of imaging modality. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). All other lesions are considered non-measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, inflammatory breast disease, and cystic lesions are all nonmeasurable.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma or renal cell carcinoma

• Metastatic brain disease

• Must have assessable target intracranial lesion(s), defined as measurable disease ≥ 10 mm in longest diameter that is not appropriate for stereotactic radiosurgery or surgical resection

• Lesions previously treated with radiosurgery AND not eligible for resection can only be used as target lesions if there has been true tumor progression on baseline scan (i.e., ≥ 20% increase in longest diameter of lesion) rather than radionecrosis

• True progression must be confirmed by PET scan or other corroborating imaging used to distinguish radionecrosis

• No leptomeningeal metastases or primary dural metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky PS 60-100%

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Total leukocyte count ≥ 3,000/mm³

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Creatinine ≤ 2.0 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 times ULN

• Hemoglobin ≥ 9.0 g/dL

• Calcium ≤ 12.0 mg/dL

• AST and ALT ≤ 1.5 times ULN

• PT ≤ 1.5 times ULN

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

• No uncontrolled medical illness including, but not limited to, any of the following:

• Hypertension (i.e., blood pressure > 150/100 mm Hg)

• Thyroid disease

• Severe valvular disease

• Severe pulmonary disease

• HIV/AIDS

• Severe psychiatric illness

• No cardiac dysrhythmia ≥ grade 2

• No prolonged QTc interval on baseline EKG

• No systemic hemorrhage ≥ grade 2 within the past 4 weeks

• No CNS hemorrhage ≥ grade 2

• Grade 1 (asymptomatic) CNS hemorrhage allowed at investigator's discretion

• None of the following within the past 6 months:

• Myocardial infarction

• Unstable angina

• Symptomatic congestive heart failure

• Stroke/transient ischemic attack

• Pulmonary embolism

• Ejection fraction ≥ 50% by baseline echocardiogram OR < 20% decrease in ejection fraction from a prior study

PRIOR CONCURRENT THERAPY:

• No prior multi-targeted tyrosine kinase inhibitor therapy (e.g., sunitinib malate or sorafenib)

• No coronary/peripheral arterial bypass surgery within the past 6 months

• More than 4 weeks since prior surgery and recovered

• More than 4 weeks since prior and no other concurrent experimental therapy or cytotoxic chemotherapy

• More than 4 weeks since prior immunotherapy

• More than 2 weeks since prior stereotactic radiosurgery and recovered

• More than 7 days since prior and no concurrent drugs that interact with CYP3A4 family, including enzyme-inducing antiepileptic drugs, warfarin, or Hypericum perforatum extract (St. John's wort)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Lauren E. Abrey, MD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Paul B. Chapman, MD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Robert J. Motzer, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00462982
• Other Study ID Numbers: 07-009; P30CA008748; MSKCC-07009
• First Posted: Apr 19, 2007
• Last Update Posted: Dec 30, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: stage IV melanoma; tumors metastatic to brain; stage IV renal cell cancer; recurrent melanoma; recurrent renal cell cancer
• Additional relevant MeSH terms: Melanoma; Kidney Neoplasms; Carcinoma, Renal Cell; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib
Arm/Group Description	Patients will be treated with 50 mg daily for four out of every six weeks.
Period Title: Overall Study
STARTED	8
COMPLETED	5
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Sunitinib
Arm/Group Description	Patients will be treated with 50 mg daily for four out of every six weeks.
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 75%
>=65 years	2 25%
Sex: Female, Male (Count of Participants)
Female	3 37.5%
Male	5 62.5%

Outcome Measures

1. Primary Outcome

Title	Central Nervous System (CNS) Response Rate by RECIST Criteria
Description	Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques (CT, MRI, X-ray) or as >10 mm with spiral CT scan. This study will use a minimum diameter of 10 mm for measurable lesions in the brain, regardless of imaging modality. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). All other lesions are considered non-measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, inflammatory breast disease, and cystic lesions are all nonmeasurable.
Time Frame	up to a year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib
Arm/Group Description	Patients will be treated with 50 mg daily for four out of every six weeks.
Measure Participants	5
Stable Disease (SD)	3 37.5%
Progression of Disease (POD)	2 25%

Adverse Events

Arm/Group Title	Sunitinib
Arm/Group Description	Patients will be treated with 50 mg daily for four out of every six weeks.
All Cause Mortality
	Sunitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Blood and lymphatic system disorders
ALT, SGPT	1/8 (12.5%)	1
AST, SGOT	1/8 (12.5%)	1
Platelets	1/8 (12.5%)	1
Cardiac disorders
Thrombosis/thrombus/embolism	2/8 (25%)	2
General disorders
Death not assoc w CTCAE term-Disease prog NOS	1/8 (12.5%)	1
Pain - Head/headache	1/8 (12.5%)	1
Nervous system disorders
Speech impairment	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	6/8 (75%)
Blood and lymphatic system disorders
ALT, SGPT	1/8 (12.5%)	1
AST, SGOT	1/8 (12.5%)	1
Hemoglobin	1/8 (12.5%)	1
Leukocytes (total WBC)	3/8 (37.5%)	3
Lymphopenia	2/8 (25%)	2
Neutrophils/granulocytes (ANC/AGC)	2/8 (25%)	2
Platelets	1/8 (12.5%)	1
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)	1/8 (12.5%)	1
Glucose, high (hyperglycemia)	2/8 (25%)	2
Metabolic/Lab - Other	1/8 (12.5%)	1
Sodium, low (hyponatremia)	1/8 (12.5%)	1
Nervous system disorders
Neuropathy: sensory	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.