Sunitinib in Treating Patients With Kidney Cancer That Cannot Be Removed by Surgery

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00459979
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 78.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

RATIONALE: Sunitinib may stop the growth of kidney cancer by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects and how well sunitinib works in treating patients with kidney cancer that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Drug: sunitinib malate; Procedure: conventional surgery	Phase 2

Detailed Description

OBJECTIVES:

• To determine the percentage of patients with renal cell carcinoma and unresectable primary tumors who can achieve sufficient tumor response, according to the operating surgeon, to undergo nephrectomy after sunitinib therapy.

• To evaluate the safety of sunitinib in patients with renal cell carcinoma and unresectable primary tumors, including analysis of the morbidity of surgery after sunitinib therapy

• To evaluate the objective response rate of patients with renal cell carcinoma and unresectable primary tumors who receive sunitinib therapy.

OUTLINE: A single arm phase II study of sunitinib in patients with unresectable renal cell carcinoma (RCC) will be conducted, including patients with and without distant metastases.

Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity. Surgery is performed if and when primary tumor becomes resectable. Patients with residual and/or metastatic disease may resume sunitinib malate within 8 weeks after surgery.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 31 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Sunitinib Malate in Patients With Renal Cell Carcinoma and Unresectable Primary Tumors
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sunitinib	Drug: sunitinib malate; Sunitinib will be dosed at 50 mg p.o. daily; Other Names: SUNITINIB L-Malate salt SU010398 PHA-290940AD Sutent SUNITINIB ; Procedure: conventional surgery; nephrectomy

Outcome Measures

Primary Outcome Measures

1. Response to Sunitinib Therapy [1 year from start of treatment]

   Defined as a reduction in tumor burden to such an extent that nephrectomy is permitted within 1 year of the start of therapy. No response to sunitinib therapy is defined as a nephrectomy not being permitted within 1 year of the start of therapy or removal from the study for any reason

Secondary Outcome Measures

1. The Number of Patients With Any Type of Complication or Adverse Event [1 year from start of treatment]

   The safety of sunitinib will be assessed by recording the number of patients with any type of complication or adverse event within 1 year of the start of therapy.

2. Progression Free Survival [1 year from start of treatment]

   Progression free survival is defined as the amount of time (in months) between the start of treatment and documented RECIST defined progression. RECIST progression is defined as at least a 20% increase in the sum of diameters of target lesions, in addition to an absolute increase of at least 5mm.

3. Percent Decrease of Diameter of Primary Tumors [1 year from start of treatment]

   Median percent decrease in size in all primary renal cell carcinoma tumors. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans.

4. Number of Tumors Which Decreased in Size [1 year from start of treatment]

   Number of tumors with at least some reduction in longest primary tumor diameter. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans.

5. Number of Tumors With 30% Reduction in Size [1 year from start of treatment]

   Number of tumors with at least 30% reduction in longest primary tumor diameter. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans.

6. Median Size Reduction Among Tumors With Some Shrinkage [1 year from start of treatment]

   The median size reduction in the largest diameter of the primary RCC tumor among the tumors with at least some shrinkage in diameter

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 confirmed renal cell carcinoma (any histology) based on prior biopsy or biopsy performed and reviewed at Cleveland Clinic Foundation. This can include pathology read as adenocarcinoma consistent with renal origin.

• Unresectable primary tumor due to any of the following factors or various combinations thereof:

• Large tumor size (> 15 cm)

• Bulky lymphadenopathy (> 4 cm or encasement of renal vessels or great vessels)

• Venous thrombosis (high level/invasive disease requiring inferior vena cava reconstruction or hypothermic circulatory arrest)

• Proximity to vital structures (e.g., mesenteric vasculature)

• Any one of these factors may or may not constitute unresectability, but for consideration for this trial, the surgical and medical oncologist must agree that the particular constellation of findings for the patient under consideration would likely entail a low probability (<50%) that the tumor would be resectable (with negative margins) or that the potential morbidity associated with an attempt at surgical resection would not be clinically acceptable. The numerical thresholds noted above are only a guideline and the clinical judgment of the surgeon and medical oncologist will determine unresectability.

• Patients with history of brain metastases can be enrolled 2 weeks following the completion of gamma knife or whole brain radiotherapy.

• ECOG performance status (PS) 0-1 or Karnofsky PS >/=70%

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

• Total Serum Bilirubin ≤ 1.5 times ULN

• Absolute neutrophil count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

• Serum calcium ≤ 12.0 mg/dL

• Creatinine ≤ 2.5 mg/dL

• 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

• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

• The presence of any of the following will exclude a patient from study enrollment:

• Prior systemic treatment for RCC.

• Evidence of bleeding diathesis or coagulopathy. Patients with hematuria from the primary renal tumor are eligible provided all other eligibility criteria are met.

• 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
• National Cancer Institute (NCI)

Investigators

• Study Chair: Brian I. Rini, MD, Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00459979
• Other Study ID Numbers: CASE17806; P30CA043703; CASE-17806; CASE-17806-CC209
• First Posted: Apr 13, 2007
• Last Update Posted: Mar 7, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by Case Comprehensive Cancer Center: clear cell renal cell carcinoma; stage III renal cell cancer; stage IV renal cell cancer; papillary renal cell carcinoma
• Additional relevant MeSH terms: Carcinoma, Renal Cell; Kidney Neoplasms; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
Period Title: Overall Study
STARTED	30
COMPLETED	28
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
Overall Participants	30
Age (Years) [Median (Full Range) ]
Median age	61 (10.0)
Sex: Female, Male (Count of Participants)
Female	9 30%
Male	21 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	28 93.3%
Unknown or Not Reported	2 6.7%
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 3.3%
White	27 90%
More than one race	0 0%
Unknown or Not Reported	2 6.7%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Response to Sunitinib Therapy
Description	Defined as a reduction in tumor burden to such an extent that nephrectomy is permitted within 1 year of the start of therapy. No response to sunitinib therapy is defined as a nephrectomy not being permitted within 1 year of the start of therapy or removal from the study for any reason
Time Frame	1 year from start of treatment

Outcome Measure Data

Analysis Population Description

per protocol - analysis after at least one cycle of Sunitinib

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
Measure Participants	28
Number [participants]	13 43.3%

2. Secondary Outcome

Title	The Number of Patients With Any Type of Complication or Adverse Event
Description	The safety of sunitinib will be assessed by recording the number of patients with any type of complication or adverse event within 1 year of the start of therapy.
Time Frame	1 year from start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
Measure Participants	28
Number [participants]	28 93.3%

3. Secondary Outcome

Title	Progression Free Survival
Description	Progression free survival is defined as the amount of time (in months) between the start of treatment and documented RECIST defined progression. RECIST progression is defined as at least a 20% increase in the sum of diameters of target lesions, in addition to an absolute increase of at least 5mm.
Time Frame	1 year from start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
Measure Participants	28
Median (Full Range) [months]	11.2

4. Secondary Outcome

Title	Percent Decrease of Diameter of Primary Tumors
Description	Median percent decrease in size in all primary renal cell carcinoma tumors. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans.
Time Frame	1 year from start of treatment

Outcome Measure Data

Analysis Population Description

per protocol - analysis after at least one cycle of Sunitinib

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
Measure Participants	28
Measure tumors	35
Median (Full Range) [percentage of tumors diameter decrease]	22

5. Secondary Outcome

Title	Number of Tumors Which Decreased in Size
Description	Number of tumors with at least some reduction in longest primary tumor diameter. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans.
Time Frame	1 year from start of treatment

Outcome Measure Data

Analysis Population Description

per protocol - after at lease one cycle of Sunitinib

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
Measure Participants	28
Measure tumors	35
Number [tumors]	28

6. Secondary Outcome

Title	Number of Tumors With 30% Reduction in Size
Description	Number of tumors with at least 30% reduction in longest primary tumor diameter. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans.
Time Frame	1 year from start of treatment

Outcome Measure Data

Analysis Population Description

per protocol- after at least one cycle of Sunitinib

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
Measure Participants	28
Measure tumors	35
Number [tumors]	13

7. Secondary Outcome

Title	Median Size Reduction Among Tumors With Some Shrinkage
Description	The median size reduction in the largest diameter of the primary RCC tumor among the tumors with at least some shrinkage in diameter
Time Frame	1 year from start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
Measure Participants	28
Measure tumors with size reduction	28
Median (Full Range) [cm]	1.6

Adverse Events

Arm/Group Title	Sunitinib
Arm/Group Description	sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy
All Cause Mortality
	Sunitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	16/28 (57.1%)
Blood and lymphatic system disorders
Hemoglobin	4/28 (14.3%)
Platelets	1/28 (3.6%)
Supraventricular and nodal arrhythmia - Atrial fibrillation	2/28 (7.1%)
Cardiac disorders
Cardiac ischemia/infarction	1/28 (3.6%)
Gastrointestinal disorders
Perforated Bowel	1/28 (3.6%)
Obstruction, GI - Small bowel NOS	1/28 (3.6%)
Pain - Abdomen NOS	3/28 (10.7%)
General disorders
Fatigue (asthenia, lethargy, malaise)	1/28 (3.6%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	1/28 (3.6%)
Death not associated with CTCAE term - Disease progression NOS	2/28 (7.1%)
"Pain - NOS	1/28 (3.6%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS	1/28 (3.6%)
Metabolism and nutrition disorders
Dehydration	1/28 (3.6%)
Sodium, serum-low (hyponatremia)	1/28 (3.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - Tumor pain	1/28 (3.6%)
Renal and urinary disorders
Obstruction, GU - Bladder	1/28 (3.6%)
Reproductive system and breast disorders
Hemorrhage, GU - Urinary NOS	3/28 (10.7%)
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory - Respiratory tract NOS	1/28 (3.6%)
Dyspnea (shortness of breath)	3/28 (10.7%)
Pleural effusion (non-malignant)	2/28 (7.1%)
Vascular disorders
Hypotension	1/28 (3.6%)
Thrombosis/thrombus/embolism	6/28 (21.4%)
Other (Not Including Serious) Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	28/28 (100%)
Blood and lymphatic system disorders
Hemoglobin	17/28 (60.7%)
Edema: head and neck	4/28 (14.3%)
Edema: limb	2/28 (7.1%)
Endocrine disorders
Thyroid function, low (hypothyroidism)	13/28 (46.4%)
Gastrointestinal disorders
Anorexia	16/28 (57.1%)
Constipation	18/28 (64.3%)
Dehydration	5/28 (17.9%)
Diarrhea	23/28 (82.1%)
Distension/bloating, abdominal	2/28 (7.1%)
Dry mouth/salivary gland (xerostomia)	3/28 (10.7%)
Gastrointestinal - Other (Specify, __)	3/28 (10.7%)
Heartburn/dyspepsia	12/28 (42.9%)
Hemorrhoids	6/28 (21.4%)
Mucositis/stomatitis (clinical exam) - Oral cavity	7/28 (25%)
Mucositis/stomatitis (functional/symptomatic) - Oral cavity	20/28 (71.4%)
Nausea	17/28 (60.7%)
Taste alteration (dysgeusia)	19/28 (67.9%)
Vomiting	12/28 (42.9%)
Hemorrhage, GI - Oral cavity	2/28 (7.1%)
Hemorrhage, GI - Rectum	6/28 (21.4%)
Pain - Abdomen NOS	9/28 (32.1%)
Pain - Dental/teeth/peridontal	2/28 (7.1%)
Pain - Oral cavity	3/28 (10.7%)
Pain - Rectum	6/28 (21.4%)
General disorders
Constitutional Symptoms - Other (Specify, __)	5/28 (17.9%)
Fatigue (asthenia, lethargy, malaise)	24/28 (85.7%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	2/28 (7.1%)
Insomnia	3/28 (10.7%)
Weight loss	4/28 (14.3%)
Pain - Other (Specify, __)	2/28 (7.1%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS	2/28 (7.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS	7/28 (25%)
Infection with unknown ANC - Dental-tooth	2/28 (7.1%)
Infection with unknown ANC - Pharynx	4/28 (14.3%)
Investigations
Leukocytes (total WBC)	12/28 (42.9%)
Lymphopenia	4/28 (14.3%)
Neutrophils/granulocytes (ANC/AGC)	12/28 (42.9%)
Platelets	22/28 (78.6%)
Alkaline phosphatase	2/28 (7.1%)
ALT, SGPT (serum glutamic pyruvic transaminase)	9/28 (32.1%)
AST, SGOT(serum glutamic oxaloacetic transaminase)	12/28 (42.9%)
Bilirubin (hyperbilirubinemia)	3/28 (10.7%)
Creatinine	11/28 (39.3%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	3/28 (10.7%)
Calcium, serum-low (hypocalcemia)	2/28 (7.1%)
Glucose, serum-high (hyperglycemia)	4/28 (14.3%)
Glucose, serum-low (hypoglycemia)	2/28 (7.1%)
Phosphate, serum-low (hypophosphatemia)	4/28 (14.3%)
Potassium, serum-high (hyperkalemia)	3/28 (10.7%)
Potassium, serum-low (hypokalemia)	3/28 (10.7%)
Sodium, serum-low (hyponatremia)	6/28 (21.4%)
Musculoskeletal and connective tissue disorders
Uric acid, serum-high (hyperuricemia)	3/28 (10.7%)
Pain - Back	4/28 (14.3%)
Pain - Chest wall	2/28 (7.1%)
Pain - Extremity-limb	12/28 (42.9%)
Pain - Joint	5/28 (17.9%)
Pain - Muscle	4/28 (14.3%)
Nervous system disorders
Dizziness	10/28 (35.7%)
Neuropathy: sensory	3/28 (10.7%)
Syncope (fainting)	2/28 (7.1%)
Pain - Head/headache	8/28 (28.6%)
Renal and urinary disorders
Hemorrhage, GU - Urinary NOS	5/28 (17.9%)
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory - Nose	8/28 (28.6%)
Hemorrhage, pulmonary/upper respiratory - Respiratory tract NOS	3/28 (10.7%)
Cough	3/28 (10.7%)
Dyspnea (shortness of breath)	6/28 (21.4%)
Hiccoughs (hiccups, singultus)	2/28 (7.1%)
Nasal cavity/paranasal sinus reactions	3/28 (10.7%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	2/28 (7.1%)
Skin and subcutaneous tissue disorders
Cheilitis	4/28 (14.3%)
Dermatology/Skin - Other	11/28 (39.3%)
Dry skin	9/28 (32.1%)
Hypopigmentation	6/28 (21.4%)
Pruritus/itching	3/28 (10.7%)
Rash/desquamation	13/28 (46.4%)
Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)	8/28 (28.6%)
Rash: hand-foot skin reaction	19/28 (67.9%)
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	3/28 (10.7%)
Vascular disorders
Hypertension	14/28 (50%)
Hypotension	4/28 (14.3%)
Hematoma	2/28 (7.1%)
Hemorrhage/Bleeding - Other	2/28 (7.1%)

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.