High-dose Bevacizumab in Advanced Renal Carcinoma Patients

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00455975
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 119
• Locations: 13
• Arms: 2
• Duration (Months): 79
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This trial will examine the effectiveness and the side effects of 2 higher dosing schedules of bevacizumab in patients that have advanced clear cell renal carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Renal Cancer; Kidney Cancer	Drug: Bevacizumab	Phase 2

Detailed Description

Bevacizumab is considered a targeted drug. Targeted drugs act on specific receptors on a cell. Bevacizumab blocks receptors that help cancer cells develop blood supplies so that the cancer can grow. These specific receptors are found in greater numbers in kidney cancer. In that regard bevacizumab will be tested in 2 doses that are higher than non-kidney cancer treatments with bevacizumab.

One group of patients will receive bevacizumab at 15 mg per kg by vein every 2 weeks. A total of 75 patients will be treated with this dose.

If this dose is well tolerated a second group of patients will receive bevacizumab at 15mg per kg by vein weekly.

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of High-Dose Bevacizumab in the Treatment of Patients With Advanced Clear Cell Renal Carcinoma
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Weekly Avastin Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity	Drug: Bevacizumab; Bevacizumab; Other Names: Avastin
Experimental: Bi-weekly Avastin Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity	Drug: Bevacizumab; Bevacizumab; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [18 months (expected)]

   Progression-free survival is measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death on study. Progression is defined in RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures

1. Overall Survival (OS) [18 months]

   Measured from date of study entry to date of death due to any cause.

2. Objective Response Rate [18 months]

   The number of patients with observed complete response [CR] or partial response [PR]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR

3. Overall Tolerability and Toxicity of High-dose Bevacizumab [18 months]

   Number of patients treated with high-dose bevacizumab experiencing Grade 3/4, treatment-related toxicities

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically documented metastatic or unresectable locally recurrent clear cell renal carcinoma

• Previous kidney removal is required except if the primary tumor was smaller than 5 cm or there was extensive liver or bone metastasis

• Patients may have received a maximum of 1 prior systemic treatment of immunotherapy (Interferon, IL-2), chemotherapy, or combination chemo+immunotherapy for metastatic disease.

• No prior bevacizumab

• Measurable disease

• Adequate liver and kidney function

• Age 18 and older

Exclusion Criteria:

• Acute MI within the past 6 months

• Uncontrolled high blood pressure or history of hypertensive crisis

• Clinically significant cardiovascular disease

• Active brain cancer

• Meningeal metastasis

• Pregnant or lactating women

• Prior treatment for another cancer less than 5 years ago

• No diseases of the central nervous system (eg. uncontrolled seizures, strokes or TIAs

• No bleeding from the mouth, rectum or coughing up blood or history of other bleeding or clotting disorders

• No history of deep vein thrombosis less than 12 months ago or are currently requiring full dose anticoagulation

• No major surgical procedures, open biopsies or traumatic injury in past 28 days

• No patients with peg tubes or feeding tubes

• No patients with non healing wounds, ulcers or long bone fractures

• No history of abdominal fistulas, gastrointestinal perforation or intrabdominal abscess within 6 months

• No symptomatic peripheral vascular disease

Please note: there are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Cancer Specialists	Fort Myers	Florida	United States	33901
2	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
3	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
4	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
5	Methodist Cancer Center	Omaha	Nebraska	United States	68114
6	Cancer Care of Western North Carolina	Asheville	North Carolina	United States	28801
7	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
8	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
9	Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
10	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee	United States	37404
11	Family Cancer Center	Collierville	Tennessee	United States	38017
12	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37023
13	Peninsula Cancer Institute	Newport News	Virginia	United States	23601

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Genentech, Inc.

Investigators

• Study Chair: John D. Hainsworth, M.D., SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00455975
• Other Study ID Numbers: SCRI GU 43; AVF 3913s
• First Posted: Apr 4, 2007
• Last Update Posted: Dec 22, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by SCRI Development Innovations, LLC: Kidney Cancer; Renal Cancer; Clear Cell Carcinoma
• Additional relevant MeSH terms: Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Bevacizumab

Study Results

Participant Flow

Arm/Group Title	Weekly Avastin	Bi-weekly Avastin
Arm/Group Description	Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity Bevacizumab: Bevacizumab	Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity Bevacizumab: Bevacizumab
Period Title: Overall Study
STARTED	58	61
COMPLETED	40	40
NOT COMPLETED	18	21

Baseline Characteristics

Arm/Group Title	Weekly Avastin	Bi-weekly Avastin	Total
Arm/Group Description	Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity Bevacizumab: Bevacizumab	Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity Bevacizumab: Bevacizumab	Total of all reporting groups
Overall Participants	58	61	119
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65	60	63
Sex: Female, Male (Count of Participants)
Female	24 41.4%	17 27.9%	41 34.5%
Male	34 58.6%	44 72.1%	78 65.5%
Region of Enrollment (participants) [Number]
United States	58 100%	61 100%	119 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Progression-free survival is measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death on study. Progression is defined in RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	18 months (expected)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Weekly Avastin	Bi-weekly Avastin
Arm/Group Description	Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity Bevacizumab: Bevacizumab	Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity Bevacizumab: Bevacizumab
Measure Participants	58	61
Median (95% Confidence Interval) [months]	6.0	5.7

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Measured from date of study entry to date of death due to any cause.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Weekly Avastin	Bi-weekly Avastin
Arm/Group Description	Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity Bevacizumab: Bevacizumab	Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity Bevacizumab: Bevacizumab
Measure Participants	58	61
Median (95% Confidence Interval) [months]	26.9	18.4

3. Secondary Outcome

Title	Objective Response Rate
Description	The number of patients with observed complete response [CR] or partial response [PR]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Weekly Avastin	Bi-weekly Avastin
Arm/Group Description	Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity Bevacizumab: Bevacizumab	Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity Bevacizumab: Bevacizumab
Measure Participants	58	61
Number [participants]	9 15.5%	6 9.8%

4. Secondary Outcome

Title	Overall Tolerability and Toxicity of High-dose Bevacizumab
Description	Number of patients treated with high-dose bevacizumab experiencing Grade 3/4, treatment-related toxicities
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients treated with Bevacizumab therapy were assessed for Grade 3/4 toxicities

Arm/Group Title	Weekly Avastin	Bi-weekly Avastin
Arm/Group Description	Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity Bevacizumab: Bevacizumab	Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity Bevacizumab: Bevacizumab
Measure Participants	58	61
Anemia	2 3.4%	5 8.2%
Thrombocytopenia	1 1.7%	0 0%
Hypertension	13 22.4%	14 23%
Proteinuria	17 29.3%	12 19.7%
Dyspnea	4 6.9%	3 4.9%
Fatigue	0 0%	4 6.6%
Nausea/vomiting	0 0%	4 6.6%
Anorexia	1 1.7%	2 3.3%
Headache	1 1.7%	1 1.6%
Confusion	0 0%	2 3.3%
Allergic/hypersensitivity reaction	1 1.7%	1 1.6%
Hemorrhage	3 5.2%	1 1.6%
Thrombosis/embolism	1 1.7%	3 4.9%
Arthralgia	1 1.7%	1 1.6%
Neuropathy/sensory	1 1.7%	0 0%
Colitis	1 1.7%	0 0%
Gastroenteritis	0 0%	1 1.6%
Renal failure	0 0%	1 1.6%
Myocardial infarction	1 1.7%	0 0%
Stroke	1 1.7%	0 0%
Tracheoesophageal fistula	1 1.7%	0 0%

Adverse Events

Arm/Group Title	Weekly Avastin		Bi-weekly Avastin
Arm/Group Description	Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity Bevacizumab: Bevacizumab		Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity Bevacizumab: Bevacizumab
All Cause Mortality
	Weekly Avastin		Bi-weekly Avastin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Weekly Avastin		Bi-weekly Avastin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/58 (56.9%)		35/61 (57.4%)
Blood and lymphatic system disorders
Anemia	1/58 (1.7%)		0/61 (0%)
Cardiac disorders
Atrial Fibrillation	0/58 (0%)		1/61 (1.6%)
Cardiac disorders - Other, ischemia	1/58 (1.7%)		0/61 (0%)
Heart Failure	0/58 (0%)		1/61 (1.6%)
Myocardial Infarction	1/58 (1.7%)		0/61 (0%)
Sinus bradycardia	1/58 (1.7%)		0/61 (0%)
Gastrointestinal disorders
Nausea	1/58 (1.7%)		1/61 (1.6%)
Abdominal pain	0/58 (0%)		1/61 (1.6%)
Vomiting	1/58 (1.7%)		1/61 (1.6%)
Colitis	0/58 (0%)		1/61 (1.6%)
Dysphagia	1/58 (1.7%)		0/61 (0%)
Esophageal fistula	1/58 (1.7%)		0/61 (0%)
Gastritis	1/58 (1.7%)		0/61 (0%)
Gastrointestinal disorders - Other, hemorrhage	1/58 (1.7%)		0/61 (0%)
Gastrointestinal disorders - Other, small bowel obstruction	0/58 (0%)		1/61 (1.6%)
General disorders
General disorders and administration site conditions - Other, disease progression	2/58 (3.4%)		2/61 (3.3%)
Non-cardiac chest pain	1/58 (1.7%)		1/61 (1.6%)
Death NOS	1/58 (1.7%)		0/61 (0%)
General disorders and administration site conditions - Other, failure to thrive	1/58 (1.7%)		0/61 (0%)
Infections and infestations
Urinary Tract Infection	0/58 (0%)		3/61 (4.9%)
Bone infection	0/58 (0%)		1/61 (1.6%)
Infections and infestations - Other, gastroenteritis	0/58 (0%)		1/61 (1.6%)
Infections and infestations - Other, pneumonia	0/58 (0%)		1/61 (1.6%)
Injury, poisoning and procedural complications
Fracture	1/58 (1.7%)		1/61 (1.6%)
Metabolism and nutrition disorders
Dehydration	2/58 (3.4%)		2/61 (3.3%)
Anorexia	1/58 (1.7%)		0/61 (0%)
Hypercalcemia	1/58 (1.7%)		0/61 (0%)
Hyperkalemia	1/58 (1.7%)		0/61 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	2/58 (3.4%)		1/61 (1.6%)
Generalized muscle weakness	2/58 (3.4%)		0/61 (0%)
Musculoskeletal and connective tissue disorders - Other, lumbar spondylosis	0/58 (0%)		1/61 (1.6%)
Nervous system disorders
Stroke	0/58 (0%)		2/61 (3.3%)
Tremor	1/58 (1.7%)		0/61 (0%)
Psychiatric disorders
Confusion	1/58 (1.7%)		1/61 (1.6%)
Psychiatric disorders - Other, change in mental status	0/58 (0%)		2/61 (3.3%)
Renal and urinary disorders
Proteinuria	0/58 (0%)		1/61 (1.6%)
Renal and urinary disorders - Other, renal failure	1/58 (1.7%)		0/61 (0%)
Urinary tract obstruction	1/58 (1.7%)		0/61 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/58 (1.7%)		1/61 (1.6%)
Pleural Effusion	1/58 (1.7%)		1/61 (1.6%)
Epistaxis	0/58 (0%)		1/61 (1.6%)
Respiratory, thoracic and mediastinal disorders - Other, chronic lung disease	0/58 (0%)		1/61 (1.6%)
Respiratory, thoracic and mediastinal disorders - Other, COPD exacerbation	0/58 (0%)		1/61 (1.6%)
Vascular disorders
Thromboembolic event	2/58 (3.4%)		1/61 (1.6%)
Hypertension	0/58 (0%)		2/61 (3.3%)
Other (Not Including Serious) Adverse Events
	Weekly Avastin		Bi-weekly Avastin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/58 (100%)		61/61 (100%)
Gastrointestinal disorders
NAUSEA	21/58 (36.2%)		22/61 (36.1%)
Constipation	10/58 (17.2%)		16/61 (26.2%)
VOMITING	8/58 (13.8%)		15/61 (24.6%)
Abdominal pain	7/58 (12.1%)		15/61 (24.6%)
Diarrhea	0/58 (0%)		16/61 (26.2%)
Oral pain	4/58 (6.9%)		6/61 (9.8%)
Mucositis	0/58 (0%)		5/61 (8.2%)
General disorders
FATIGUE	37/58 (63.8%)		50/61 (82%)
Fever	5/58 (8.6%)		11/61 (18%)
Edema limbs	0/58 (0%)		13/61 (21.3%)
Chills	4/58 (6.9%)		6/61 (9.8%)
Edema	4/58 (6.9%)		5/61 (8.2%)
Non-cardiac chest pain	1/58 (1.7%)		7/61 (11.5%)
Immune system disorders
Allergic reaction	4/58 (6.9%)		9/61 (14.8%)
Infections and infestations
Rhinitis infective	2/58 (3.4%)		3/61 (4.9%)
Investigations
Creatinine increased	0/58 (0%)		9/61 (14.8%)
Alkaline phosphatase increased	0/58 (0%)		6/61 (9.8%)
Weight loss	0/58 (0%)		5/61 (8.2%)
Metabolism and nutrition disorders
Anorexia	14/58 (24.1%)		24/61 (39.3%)
Hyperglycemia	6/58 (10.3%)		11/61 (18%)
hyperkalemia	0/58 (0%)		11/61 (18%)
Hypercalcemia	5/58 (8.6%)		5/61 (8.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/58 (20.7%)		19/61 (31.1%)
Pain in extremity	9/58 (15.5%)		21/61 (34.4%)
ARTHRALGIA	5/58 (8.6%)		13/61 (21.3%)
Myalgia	5/58 (8.6%)		11/61 (18%)
Back pain	9/58 (15.5%)		0/61 (0%)
Bone pain	0/58 (0%)		7/61 (11.5%)
Generalized muscle weakness	5/58 (8.6%)		0/61 (0%)
Nervous system disorders
HEADACHE	18/58 (31%)		17/61 (27.9%)
Dizziness	0/58 (0%)		12/61 (19.7%)
Peripheral sensory neuropathy	0/58 (0%)		8/61 (13.1%)
Tremor	3/58 (5.2%)		2/61 (3.3%)
Psychiatric disorders
Insomnia	4/58 (6.9%)		9/61 (14.8%)
Depression	3/58 (5.2%)		6/61 (9.8%)
Renal and urinary disorders
PROTEINURIA	34/58 (58.6%)		39/61 (63.9%)
Renal and urinary disorders - Other, urinary hemorrhage	3/58 (5.2%)		5/61 (8.2%)
Respiratory, thoracic and mediastinal disorders
DYSPNEA	16/58 (27.6%)		17/61 (27.9%)
Cough	0/58 (0%)		15/61 (24.6%)
Epistaxis	0/58 (0%)		10/61 (16.4%)
Voice alteration	0/58 (0%)		7/61 (11.5%)
Respiratory, thoracic and mediastinal disorders - Other, sinus drainage	0/58 (0%)		7/61 (11.5%)
Skin and subcutaneous tissue disorders
Rash	8/58 (13.8%)		12/61 (19.7%)
Hyperhidrosis	3/58 (5.2%)		6/61 (9.8%)
Vascular disorders
HYPERTENSION	30/58 (51.7%)		0/61 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.