Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ziv-Aflibercept in Treating Patients With Metastatic or Unresectable Kidney Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00357760
Recruitment Status : Completed
First Posted : July 27, 2006
Results First Posted : April 4, 2017
Last Update Posted : June 23, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Renal Cell Carcinoma
Intervention Biological: VEGF Trap
Enrollment 94
Recruitment Details The study was activated on 12/21/2007 and closed to accrual on 12/6/2013 with a total accrual of 94 patients.
Pre-assignment Details  
Arm/Group Title Arm A (Higher Dose of VEGF Trap) Arm B (Lower Dose of VEGF Trap)
Hide Arm/Group Description Patients receive a higher dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients receive a lower dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, the dose of ziv-aflibercept (VEGF Trap) may be escalated to the higher dose in Arm A.
Period Title: Overall Study
Started 59 35
Patients Who Started Treatment 57 34
Eligible and Treated Patients 57 32
Patients Who Undergo Dose Escalation 0 [1] 16
Completed 0 [2] 0 [2]
Not Completed 59 35
Reason Not Completed
Disease progression             44             17
Adverse Event             10             7
Death             0             3
Alternative therapy             1             0
Withdrawal by Subject             0             2
Never started treatment             2             1
Ineligible             0             2
Physician Decision             2             1
Protocol Violation             0             1
To receive hospice care             0             1
[1]
Only patients who progressed on the low dose (Arm B) had the opportunity to undergo dose escalation.
[2]
Patients continued receiving protocol treatment until progressive disease or unacceptable toxicity.
Arm/Group Title Arm A (Higher Dose of VEGF Trap) Arm B (Lower Dose of VEGF Trap) Total
Hide Arm/Group Description Patients receive a higher dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients receive a lower dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, the dose of ziv-aflibercept (VEGF Trap) may be escalated to the higher dose in Arm A. Total of all reporting groups
Overall Number of Baseline Participants 57 32 89
Hide Baseline Analysis Population Description
Eligible and treated patients are included in this analysis.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 57 participants 32 participants 89 participants
60
(35 to 80)
62
(33 to 73)
61
(33 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 32 participants 89 participants
Female
14
  24.6%
10
  31.3%
24
  27.0%
Male
43
  75.4%
22
  68.8%
65
  73.0%
1.Primary Outcome
Title Proportion of Patients Alive and Progression-free at 8 Weeks
Hide Description

Progression-free survival (PFS) was defined as time from randomization to the earlier of documentation of progression or death. The proportion of patients who are progression-free and alive at 8 weeks was estimated using the Kaplan-Meier method and the confidence interval was estimated using log transformation method.

Progression is defined using Response Evaluation Criteria In Solid Tumors (RECIST), as a 20% increase in the sum of the longest diameters of target lesions, or the appearance of new lesions, or unequivocal progression of existing nontarget lesions.

Time Frame Assessed at 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible and treated patients are included in this analysis.
Arm/Group Title Arm A (Higher Dose of VEGF Trap) Arm B (Lower Dose of VEGF Trap)
Hide Arm/Group Description:
Patients receive a higher dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Patients receive a lower dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, the dose of ziv-aflibercept (VEGF Trap) may be escalated to the higher dose in Arm A.
Overall Number of Participants Analyzed 57 32
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.70
(0.59 to 0.79)
0.52
(0.37 to 0.66)
2.Secondary Outcome
Title Proportion of Patients With Objective Response
Hide Description

Objective response is defined as complete response (CR) or partial response (PR) determined by Solid Tumor Response Criteria (RECIST).

CR: The disappearance of all target lesions without the appearance of new lesion(s) and/or unequivocal progression of existing non-target lesions.

PR: At least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter without the appearance of new lesion(s) and/or unequivocal progression of existing non-target lesions.

To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met.

Time Frame Assessed every 8 weeks while on treatment and then every 3 months until patient is 2 years from enrollment, and then every 6 months until patient is 3 years from enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible and treated patients are included in this analysis.
Arm/Group Title Arm A (Higher Dose of VEGF Trap) Arm B (Lower Dose of VEGF Trap)
Hide Arm/Group Description:
Patients receive a higher dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Patients receive a lower dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, the dose of ziv-aflibercept (VEGF Trap) may be escalated to the higher dose in Arm A.
Overall Number of Participants Analyzed 57 32
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.053
(0.014 to 0.13)
0.031
(0.002 to 0.14)
3.Secondary Outcome
Title Progression-free Survival (PFS) Among Patients Who Undergo Dose Escalation Following Progression on Lower-dose VEGF Trap
Hide Description

Patients who progressed on the 1 mg/kg dose (Arm B) at 8 weeks would have the opportunity to receive the 4 mg/kg dose. PFS is defined as the time from dose escalation to disease progression or death, whichever occurs first.

Disease progression is defined using Response Evaluation Criteria In Solid Tumors (RECIST), as a 20% increase in the sum of the longest diameters of target lesions, or the appearance of new lesions, or unequivocal progression of existing nontarget lesions.

Time Frame Assessed every 8 weeks while on treatment and then every 3 months until patient is 2 years from enrollment, and then every 6 months until patient is 3 years from enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients who progressed on the low dose (Arm B) and underwent dose escalation were included in this analysis.
Arm/Group Title Arm A (Higher Dose of VEGF Trap) Arm B (Lower Dose of VEGF Trap)
Hide Arm/Group Description:
Patients receive a higher dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Patients receive a lower dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, the dose of ziv-aflibercept (VEGF Trap) may be escalated to the higher dose in Arm A.
Overall Number of Participants Analyzed 0 16
Median (90% Confidence Interval)
Unit of Measure: weeks
14.57
(7.57 to 33.00)
4.Other Pre-specified Outcome
Title Circulating Levels of VEGF-Trap Complex
Hide Description [Not Specified]
Time Frame Assessed at baseline, 4 weeks, 6 weeks, 8 weeks and end of treatment
Outcome Measure Data Not Reported
5.Other Pre-specified Outcome
Title Angiogenesis-related Protein Expression
Hide Description [Not Specified]
Time Frame Assessed every 8 weeks during treatment and end of treatment
Outcome Measure Data Not Reported
Time Frame Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, assessed up to 3 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A (Higher Dose of VEGF Trap) Arm B (Lower Dose of VEGF Trap)
Hide Arm/Group Description Patients receive a higher dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients receive a lower dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, the dose of ziv-aflibercept (VEGF Trap) may be escalated to the higher dose in Arm A.
All-Cause Mortality
Arm A (Higher Dose of VEGF Trap) Arm B (Lower Dose of VEGF Trap)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Arm A (Higher Dose of VEGF Trap) Arm B (Lower Dose of VEGF Trap)
Affected / at Risk (%) Affected / at Risk (%)
Total   35/57 (61.40%)   18/34 (52.94%) 
Blood and lymphatic system disorders     
Anemia  1  2/57 (3.51%)  3/34 (8.82%) 
Cardiac disorders     
Supraventricular tachycardia  1  0/57 (0.00%)  1/34 (2.94%) 
Cardiac-ischemia  1  1/57 (1.75%)  0/34 (0.00%) 
Pericardial effusion (non-malignant)  1  1/57 (1.75%)  0/34 (0.00%) 
Gastrointestinal disorders     
Esophagitis  1  0/57 (0.00%)  1/34 (2.94%) 
Abdomen, pain  1  2/57 (3.51%)  0/34 (0.00%) 
General disorders     
Fatigue  1  2/57 (3.51%)  7/34 (20.59%) 
Immune system disorders     
Cytokine release syndrome  1  1/57 (1.75%)  0/34 (0.00%) 
Infections and infestations     
Infection Gr0-2 neut, urinary tract  1  1/57 (1.75%)  0/34 (0.00%) 
Investigations     
Cardiac troponin I (cTnI) increased  1  0/57 (0.00%)  1/34 (2.94%) 
Metabolism and nutrition disorders     
Anorexia  1  1/57 (1.75%)  0/34 (0.00%) 
Hypoalbuminemia  1  0/57 (0.00%)  1/34 (2.94%) 
Hypophosphatemia  1  0/57 (0.00%)  1/34 (2.94%) 
Hypokalemia  1  1/57 (1.75%)  0/34 (0.00%) 
Hyponatremia  1  2/57 (3.51%)  0/34 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back, pain  1  0/57 (0.00%)  1/34 (2.94%) 
Bone, pain  1  0/57 (0.00%)  1/34 (2.94%) 
Muscle, pain  1  0/57 (0.00%)  1/34 (2.94%) 
Nervous system disorders     
CNS, hemorrhage  1  0/57 (0.00%)  1/34 (2.94%) 
Cognitive disturbance  1  1/57 (1.75%)  0/34 (0.00%) 
Encephalopathy  1  1/57 (1.75%)  0/34 (0.00%) 
Head/headache  1  2/57 (3.51%)  0/34 (0.00%) 
Renal and urinary disorders     
Urinary hemorrhage NOS  1  0/57 (0.00%)  1/34 (2.94%) 
Glomerular filtration rate decreased  1  0/57 (0.00%)  1/34 (2.94%) 
Proteinuria  1  9/57 (15.79%)  2/34 (5.88%) 
Renal/GU-other  1  0/57 (0.00%)  1/34 (2.94%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  3/57 (5.26%)  1/34 (2.94%) 
Vascular disorders     
Hypertension  1  20/57 (35.09%)  5/34 (14.71%) 
Hypotension  1  1/57 (1.75%)  0/34 (0.00%) 
Thrombosis/thrombus/embolism  1  3/57 (5.26%)  0/34 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE 3.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A (Higher Dose of VEGF Trap) Arm B (Lower Dose of VEGF Trap)
Affected / at Risk (%) Affected / at Risk (%)
Total   52/57 (91.23%)   33/34 (97.06%) 
Blood and lymphatic system disorders     
Anemia  1  11/57 (19.30%)  11/34 (32.35%) 
Hemolysis  1  5/57 (8.77%)  0/34 (0.00%) 
Gastrointestinal disorders     
Constipation  1  11/57 (19.30%)  10/34 (29.41%) 
Diarrhea w/o prior colostomy  1  11/57 (19.30%)  8/34 (23.53%) 
Dry mouth  1  4/57 (7.02%)  1/34 (2.94%) 
Dyspepsia  1  1/57 (1.75%)  2/34 (5.88%) 
Muco/stomatitis by exam, oral cavity  1  0/57 (0.00%)  4/34 (11.76%) 
Muco/stomatitis (symptom) oral cavity  1  5/57 (8.77%)  6/34 (17.65%) 
Nausea  1  11/57 (19.30%)  17/34 (50.00%) 
Vomiting  1  1/57 (1.75%)  6/34 (17.65%) 
Abdomen, pain  1  0/57 (0.00%)  2/34 (5.88%) 
General disorders     
Fatigue  1  36/57 (63.16%)  24/34 (70.59%) 
Fever w/o neutropenia  1  1/57 (1.75%)  2/34 (5.88%) 
Rigors/chills  1  0/57 (0.00%)  3/34 (8.82%) 
Edema limb  1  4/57 (7.02%)  5/34 (14.71%) 
Chest/thoracic pain NOS  1  2/57 (3.51%)  3/34 (8.82%) 
Pain-other  1  5/57 (8.77%)  0/34 (0.00%) 
Investigations     
Leukocytes decreased  1  5/57 (8.77%)  1/34 (2.94%) 
Neutrophils decreased  1  2/57 (3.51%)  2/34 (5.88%) 
Platelets decreased  1  5/57 (8.77%)  3/34 (8.82%) 
Weight loss  1  7/57 (12.28%)  4/34 (11.76%) 
Alkaline phosphatase increased  1  4/57 (7.02%)  5/34 (14.71%) 
Alanine aminotransferase increased  1  6/57 (10.53%)  1/34 (2.94%) 
Aspartate aminotransferase increased  1  4/57 (7.02%)  3/34 (8.82%) 
Creatinine increased  1  8/57 (14.04%)  6/34 (17.65%) 
Metabolism and nutrition disorders     
Anorexia  1  22/57 (38.60%)  16/34 (47.06%) 
Hypoalbuminemia  1  6/57 (10.53%)  2/34 (5.88%) 
Hypercalcemia  1  0/57 (0.00%)  3/34 (8.82%) 
Hypocalcemia  1  2/57 (3.51%)  2/34 (5.88%) 
Hyperglycemia  1  3/57 (5.26%)  5/34 (14.71%) 
Hypophosphatemia  1  4/57 (7.02%)  1/34 (2.94%) 
Hyperkalemia  1  2/57 (3.51%)  4/34 (11.76%) 
Hyponatremia  1  7/57 (12.28%)  7/34 (20.59%) 
Musculoskeletal and connective tissue disorders     
Back, pain  1  0/57 (0.00%)  3/34 (8.82%) 
Extremity-limb, pain  1  0/57 (0.00%)  2/34 (5.88%) 
Joint, pain  1  11/57 (19.30%)  8/34 (23.53%) 
Muscle, pain  1  4/57 (7.02%)  3/34 (8.82%) 
Nervous system disorders     
Taste disturbance  1  4/57 (7.02%)  3/34 (8.82%) 
Dizziness  1  5/57 (8.77%)  1/34 (2.94%) 
Neuropathy-sensory  1  2/57 (3.51%)  4/34 (11.76%) 
Head/headache  1  17/57 (29.82%)  8/34 (23.53%) 
Psychiatric disorders     
Anxiety  1  0/57 (0.00%)  2/34 (5.88%) 
Renal and urinary disorders     
Proteinuria  1  25/57 (43.86%)  20/34 (58.82%) 
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis  1  3/57 (5.26%)  1/34 (2.94%) 
Nose, hemorrhage  1  3/57 (5.26%)  6/34 (17.65%) 
Pleura, hemorrhage  1  4/57 (7.02%)  2/34 (5.88%) 
Cough  1  8/57 (14.04%)  6/34 (17.65%) 
Dyspnea  1  8/57 (14.04%)  12/34 (35.29%) 
Nasal cavity/paranasal sinus reaction  1  4/57 (7.02%)  0/34 (0.00%) 
Voice changes/dysarthria  1  12/57 (21.05%)  10/34 (29.41%) 
Skin and subcutaneous tissue disorders     
Sweating  1  2/57 (3.51%)  2/34 (5.88%) 
Alopecia  1  3/57 (5.26%)  1/34 (2.94%) 
Rash: acne/acneiform  1  4/57 (7.02%)  2/34 (5.88%) 
Hand-foot reaction  1  3/57 (5.26%)  1/34 (2.94%) 
Vascular disorders     
Hypertension  1  22/57 (38.60%)  10/34 (29.41%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE 3.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Statistician
Organization: ECOG-ACRIN Statistical Office
Phone: 617-632-3012
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00357760    
Other Study ID Numbers: NCI-2009-00559
NCI-2009-00559 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
E4805 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
U10CA180820 ( U.S. NIH Grant/Contract )
U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted: July 26, 2006
First Posted: July 27, 2006
Results First Submitted: February 8, 2017
Results First Posted: April 4, 2017
Last Update Posted: June 23, 2017