Sunitinib Malate in Treating Patients With Previously Untreated Metastatic Kidney Cancer

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01158222
• Collaborator: (none)
• Enrollment: 37
• Location: 1
• Arm: 1
• Actual Duration (Months): 77.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib malate it works in treating patients with previously untreated metastatic kidney cancer.

Condition or Disease	Intervention/Treatment	Phase
Clear Cell Renal Cell Carcinoma; Stage IV Renal Cell Cancer	Drug: sunitinib malate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the feasibility of intermittent sunitinib therapy in patients with metastatic renal cell carcinoma (RCC).

SECONDARY OBJECTIVES:

1. To determine the clinical outcome (response rate and overall progression-free survival) in metastatic renal cell carcinoma patients treated with intermittent sunitinib therapy.

2. To evaluate the toxicity of intermittent sunitinib therapy in patients with metastatic renal cell carcinoma.

3. To assess the feasibility of detecting circulating tumor cells (CTCs) in RCC patients and investigate the association between the VEGF -634 genotype and the occurrence of hypertension in sunitinib-treated RCC patients.

OUTLINE:

Patients receive oral sunitinib malate once daily on days 1-28. Sunitinib dosing schedule may be changed to 14 days on followed by 7 days off, and repeated for a 6-week cycle, at the discretion of the treating physician for toxicity purposes. Cycles will be defined as 6 week intervals regardless of dosing interruptions. All patients will be treated for 4 cycles in the absence of unacceptable toxicity or RECIST-defined progressive disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients With Metastatic Renal Cell Carcinoma
• Actual Study Start Date: Aug 18, 2010
• Actual Primary Completion Date: Jun 20, 2013
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: sunitinib malate; Given orally; Other Names: SU011248 SU11248 sunitinib Sutent

Outcome Measures

Primary Outcome Measures

1. Feasibility as Assessed by Proportion of Patients Eligible for Intermittent Therapy Who Actually Receive it [after 6 months of treatment (4 cycles)]

   Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.

Secondary Outcome Measures

1. Change in Circulating Tumor Cells [Pre-treatment, day 1, and day 28 of every cycle]

2. Relationship Between Hypertension and Germline VEGF Single Nucleotide Polymorphism (SNP) -634 Genotype [Day 28 of each cycle]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically-proven advanced RCC with a component of clear cell histology

• Measurable disease per RECIST criteria

• ECOG performance status 0-1

• Prior nephrectomy is NOT required

• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x laboratory upper limit of normal (ULN)

• Total serum bilirubin ≤ 2.0 x ULN

• Absolute neutrophil count (ANC) ≥ 1500/uL

• Platelets ≥ 100,000/uL

• Hemoglobin ≥ 8.0 g/dL (transfusion permitted)

• Serum calcium ≤ 12.0 mg/dL

• Serum creatinine ≤ 2.5 mg/dL

• Patients with history of brain metastases can be enrolled at a minimum of 2 weeks following the completion of surgery, gamma knife or whole brain radiotherapy; repeat brain MRI not required for eligibility

• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment

Exclusion Criteria:

• Prior systemic treatment for advanced RCC. Prior adjuvant therapy (any drug) is allowed if end of adjuvant therapy was more than 1 year prior to start of sunitinib on this protocol.

• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass graft, New York Heart Association grade II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically significant bleeding or pulmonary embolism

• Hypertension that cannot be controlled by medications to < 160/90 mmHg

• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness

• Pregnancy or breastfeeding

• Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Case Comprehensive Cancer Center

Investigators

• Principal Investigator: Brian Rini, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01158222
• Other Study ID Numbers: CASE8809; NCI-2010-01391
• First Posted: Jul 8, 2010
• Last Update Posted: Sep 14, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Sunitinib

Study Results

Participant Flow

Pre-assignment Detail	5 additional patients were consented but not enrolled in the study. No information was collected on them and they are not included in the patient flow. Demographics information was not collected on these patients.

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally laboratory biomarker analysis: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies polymorphism analysis: Correlative studies
Period Title: Overall Study
STARTED	37
COMPLETED	20
NOT COMPLETED	17

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally laboratory biomarker analysis: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies polymorphism analysis: Correlative studies
Overall Participants	37
Age, Customized (Count of Participants)
40-49	3 8.1%
50-59	9 24.3%
60-69	18 48.6%
70-79	6 16.2%
80-89	1 2.7%
Sex: Female, Male (Count of Participants)
Female	11 29.7%
Male	26 70.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	35 94.6%
Unknown or Not Reported	2 5.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 2.7%
White	34 91.9%
More than one race	0 0%
Unknown or Not Reported	2 5.4%
Region of Enrollment (participants) [Number]
United States	37 100%

Outcome Measures

1. Primary Outcome

Title	Feasibility as Assessed by Proportion of Patients Eligible for Intermittent Therapy Who Actually Receive it
Description	Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.
Time Frame	after 6 months of treatment (4 cycles)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally laboratory biomarker analysis: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies polymorphism analysis: Correlative studies
Measure Participants	20
Count of Participants [Participants]	20 54.1%

2. Secondary Outcome

Title	Change in Circulating Tumor Cells
Time Frame	Pre-treatment, day 1, and day 28 of every cycle

Outcome Measure Data

Analysis Population Description

Did not complete this analysis. Data not collected.

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally laboratory biomarker analysis: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies polymorphism analysis: Correlative studies
Measure Participants	0

3. Secondary Outcome

Title	Relationship Between Hypertension and Germline VEGF Single Nucleotide Polymorphism (SNP) -634 Genotype
Time Frame	Day 28 of each cycle

Outcome Measure Data

Analysis Population Description

Did not complete this analysis. Data not collected.

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally laboratory biomarker analysis: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies polymorphism analysis: Correlative studies
Measure Participants	0

Adverse Events

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally laboratory biomarker analysis: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies polymorphism analysis: Correlative studies
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	2/37 (5.4%)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	13/37 (35.1%)
Cardiac disorders
Atrial Fibrillation	1/37 (2.7%)	1
Gastrointestinal disorders
Abdominal Pain	2/37 (5.4%)	2
Diarrhea	1/37 (2.7%)	1
Gastrointestinal disorder - other	1/37 (2.7%)	1
General disorders
Chills	1/37 (2.7%)	1
Edema Trunk	1/37 (2.7%)	1
Fever	1/37 (2.7%)	1
Infections and infestations
Abdominal infection	1/37 (2.7%)	1
Infection and infestation - other	1/37 (2.7%)	1
Lung infection	1/37 (2.7%)	1
Upper respiratory infection	2/37 (5.4%)	2
Urinary tract infection	1/37 (2.7%)	1
Investigations
Weight Gain	1/37 (2.7%)	1
Metabolism and nutrition disorders
Hyperkalemia	1/37 (2.7%)	1
Nervous system disorders
Intracranial Hemorrhage	1/37 (2.7%)	1
Syncope	1/37 (2.7%)	2
Renal and urinary disorders
Hematuria	1/37 (2.7%)	1
Proteinuria	1/37 (2.7%)	1
Renal and urinary disorders - other	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/37 (2.7%)	2
Respiratory, thoracic and mediastinal disorders - other	1/37 (2.7%)	1
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysesthesia Syndrome	1/37 (2.7%)	1
Vascular disorders
Thromboembolic Event	1/37 (2.7%)	1
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	37/37 (100%)
Blood and lymphatic system disorders
Anemia	26/37 (70.3%)	67
Blood and lymphatic system disorders - other	2/37 (5.4%)	2
Endocrine disorders
Hyperthyroidism	3/37 (8.1%)	3
Hypothyroidism	18/37 (48.6%)	24
Gastrointestinal disorders
Abdominal distension	2/37 (5.4%)	2
Abdominal Pain	9/37 (24.3%)	12
Cheilitis	4/37 (10.8%)	7
Constipation	18/37 (48.6%)	32
Dental Caries	2/37 (5.4%)	2
Diarrhea	23/37 (62.2%)	88
Dry Mouth	4/37 (10.8%)	5
Dyspepsia	19/37 (51.4%)	35
Flatulence	3/37 (8.1%)	4
Gastroesophageal Reflux Disease	5/37 (13.5%)	6
Gastrointestinal Disorders - Other	4/37 (10.8%)	9
Hemorrhoidal hemorrhage	6/37 (16.2%)	6
Hemorrhoids	7/37 (18.9%)	7
Lip Pain	2/37 (5.4%)	2
Mucositis Oral	31/37 (83.8%)	107
Nausea	25/37 (67.6%)	75
Oral Hemorrhage	3/37 (8.1%)	3
Oral Pain	3/37 (8.1%)	5
Vomiting	13/37 (35.1%)	25
General disorders
Chills	3/37 (8.1%)	5
Edema limbs	11/37 (29.7%)	15
Fatigue	35/37 (94.6%)	127
Fever	4/37 (10.8%)	8
General Disorders - Other	4/37 (10.8%)	4
Localized Edema	2/37 (5.4%)	3
Pain	15/37 (40.5%)	35
Infections and infestations
Lung Infection	2/37 (5.4%)	2
Mucosal Infection	2/37 (5.4%)	3
Nail Infection	2/37 (5.4%)	2
Pharyngitis	3/37 (8.1%)	3
Rhinitis Infective	2/37 (5.4%)	2
Skin Infection	2/37 (5.4%)	9
Tooth Infection	2/37 (5.4%)	4
Upper Respiratory Infection	5/37 (13.5%)	6
Urinary Tract Infection	4/37 (10.8%)	5
Injury, poisoning and procedural complications
Bruising	3/37 (8.1%)	6
Investigations
Alanine Aminotransferase Increased	10/37 (27%)	18
Alkaline Phosphatase Increased	3/37 (8.1%)	5
Aspartate Aminotranferase Increased	13/37 (35.1%)	34
Blood Bilirubin Increased	4/37 (10.8%)	7
Creatinine Increased	17/37 (45.9%)	39
Lymphocyte Count Decreased	4/37 (10.8%)	6
Neutrophil Count Decreased	18/37 (48.6%)	57
Platelet Count Decreased	31/37 (83.8%)	115
Weight Gain	3/37 (8.1%)	6
Weight Loss	14/37 (37.8%)	16
White Blood Cell Decreased	25/37 (67.6%)	73
Metabolism and nutrition disorders
Anorexia	19/37 (51.4%)	53
Dehydration	5/37 (13.5%)	5
Hypercalcemia	2/37 (5.4%)	3
Hyperclycemia	8/37 (21.6%)	18
Hyperkalemia	6/37 (16.2%)	11
Hyperuricemia	3/37 (8.1%)	5
Hypoalbuminemia	5/37 (13.5%)	12
Hypocalcemia	2/37 (5.4%)	4
Hypokalemia	2/37 (5.4%)	4
Hypomagnesemia	4/37 (10.8%)	4
Hyponatremia	10/37 (27%)	32
Hypophosphatemia	5/37 (13.5%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	9/37 (24.3%)	121
Arthritis	2/37 (5.4%)	3
Back Pain	5/37 (13.5%)	5
Generalized Muscle Weakness	4/37 (10.8%)	11
Muscle Weakness Lower Limb	2/37 (5.4%)	3
Myalgia	9/37 (24.3%)	20
Pain in Extremity	11/37 (29.7%)	17
Bone Pain	3/37 (8.1%)	8
Nervous system disorders
Cognitive Disturbance	4/37 (10.8%)	4
Dizziness	6/37 (16.2%)	6
Dysgeusia	26/37 (70.3%)	58
Headache	10/37 (27%)	21
Syncope	2/37 (5.4%)	2
Psychiatric disorders
Anxiety	4/37 (10.8%)	4
Depression	5/37 (13.5%)	6
Insomnia	3/37 (8.1%)	3
Renal and urinary disorders
Hematuria	2/37 (5.4%)	3
Respiratory, thoracic and mediastinal disorders
Cough	7/37 (18.9%)	9
Dyspnea	3/37 (8.1%)	3
Epistaxis	7/37 (18.9%)	12
Sore Throat	2/37 (5.4%)	5
Voice Alteration	3/37 (8.1%)	3
Skin and subcutaneous tissue disorders
Alopecia	4/37 (10.8%)	4
Dry Skin	14/37 (37.8%)	22
Erythema Multiforme	6/37 (16.2%)	11
Erythroderma	2/37 (5.4%)	2
Pain of Skin	4/37 (10.8%)	5
Palmar-plantar Erythrodysesthesia Syndrome	20/37 (54.1%)	78
Pruritus	8/37 (21.6%)	13
Purpura	8/37 (21.6%)	18
Rash Acneiform	10/37 (27%)	19
Scalp Pain	2/37 (5.4%)	2
Skin and Subcutaneous Tissue Disorders - Other	4/37 (10.8%)	12
Skin and Subcutaneous Tissue Disorders - Other	6/37 (16.2%)	10
Vascular disorders
Hot Flashes	3/37 (8.1%)	3
Hypertension	22/37 (59.5%)	45

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.