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CCI-779 and Bevacizumab 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: NCT00112840
Recruitment Status : Completed
First Posted : June 3, 2005
Results First Posted : September 11, 2014
Last Update Posted : November 16, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Interventions Drug: CCI-779
Drug: Bevacizumab
Enrollment 60
Recruitment Details From 5/11/2005 to 7/19/2006, 14 participants were registered to the Phase I portion of the study (8 at Dose Level 1 and 6 at Dose Level 2). Phase II opened 02/09/2007 at Dose Level 2 and registered 46 patients before closing with full accrual on 6/15/2010.
Pre-assignment Details In Phase I, Dose Level 2, 2 subjects were unevaluable because they were removed from the study before completing cycle 1 of treatment for reasons other than toxicity. In Phase II, 5/46 patients were ineligible and one patient cancelled.
Arm/Group Title Phase I, Dose Level 1 Phase I, Dose Level 2 Phase II
Hide Arm/Group Description Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 In the Phase 1, Dose Level 1 portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and IV Bevacizumab (level 1=5mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 In the Phase 1, Dose Level 2 portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and IV Bevacizumab (level 1= 10 mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Phase II patients were treated at the highest dose level (dose level 2: CCI-779 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). Patients receive 25 mg CCI-779 IV on days 1, 8, 15, and 22 and 10 mg/kg bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Period Title: Overall Study
Started 8 6 46
Completed 6 6 40
Not Completed 2 0 6
Reason Not Completed
Physician Decision             1             0             0
Withdrawal by Subject             1             0             1
Protocol Violation             0             0             5
Arm/Group Title Phase I, Dose Level 1 Phase I, Dose Level 2 Phase II Total
Hide Arm/Group Description Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 In the Phase 1, Dose Level 1 portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and IV Bevacizumab (level 1=5mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 In the Phase 1, Dose Level 2 portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and IV Bevacizumab (level 1=5mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Phase II patients were treated at the highest dose level (dose level 2: CCI-779 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). Patients receive 25 mg CCI-779 IV on days 1, 8, 15, and 22 and 10 mg/kg bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry. Total of all reporting groups
Overall Number of Baseline Participants 8 6 46 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 8 participants 6 participants 46 participants 60 participants
61
(44 to 75)
66
(61 to 77)
62
(38 to 82)
62.5
(38 to 82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 46 participants 60 participants
Female
1
  12.5%
1
  16.7%
11
  23.9%
13
  21.7%
Male
7
  87.5%
5
  83.3%
35
  76.1%
47
  78.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 8 participants 6 participants 46 participants 60 participants
8 6 46 60
1.Primary Outcome
Title Dose-limiting Toxicity (DLT) (Phase I)
Hide Description

For this protocol, dose limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment in the first four weeks of combination therapy, and meeting the following criteria:

  • Grade 4 Absolute neutrophil count (ANC) for 5+ days.
  • Grade 4 anemia or thrombocytopenia of any duration.
  • Serum Creatinine 2 times baseline or 2x upper limit of normal if baseline levels not normal.
  • Any other non-hematologic grade 3 or higher as per NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 3.0, except fatigue and grade 3 Hypertension that is will be controlled with oral medication.
  • Grade 3 triglycerides will be a DLT for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy.

The maximum tolerated dose level (MTD) will be defined as the highest safely tolerated dose where 1 or 0 out of 6 patients experience DLT with the next higher dose.

Time Frame Patients observed a minimum of 4 weeks (one full course). The maximum number of cycles observed was 16 cycles.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I, Dose Level 1 Phase 1 , Dose Level 2 Phase II
Hide Arm/Group Description:
Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 in escalating dose levels to determine Maximum Tolerated Dose (MTD). In the phase I portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. The first three patients began at dose level 1 and cohort doses escalate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 In the Phase 1, Dose Level 2 portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and IV Bevacizumab (level 1=10 mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Phase II patients were treated at the highest dose level (dose level 2: CCI-779 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). Patients receive 25 mg CCI-779 IV on days 1, 8, 15, and 22 and 10 mg/kg bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Overall Number of Participants Analyzed 6 6 0
Measure Type: Number
Unit of Measure: participants
1 1
2.Primary Outcome
Title Proportion of Progression-free Patients at 6 Months (Phase II)
Hide Description Determination of progression will be made according to Response Evaluation Criteria in Solid Tumors (RECIST). A progression (PD) is defined as having at least a 20% increase in the sum of the longest dimension of target lesions taking as reference the smallest sum of the largest dimension recorded at baseline.The proportion of progression-free patients will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the success proportion will be calculated. All patients meeting the eligibility criteria who have signed a consent form and begun treatment will be considered evaluable. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred.
Time Frame 6 months after study entry
Hide Outcome Measure Data
Hide Analysis Population Description
Only Phase II participants were analyzed for this endpoint. Forty participants from Phase II were evaluable for this endpoint.
Arm/Group Title Phase I, Dose Level 1 Phase 1, Dose Level 2 Phase II
Hide Arm/Group Description:
Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 in escalating dose levels to determine Maximum Tolerated Dose (MTD). In the phase I portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. The first three patients began at dose level 1 and cohort doses escalate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 In the Phase 1, Dose Level 2 portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and IV Bevacizumab (level 1=10 mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Phase II patients were treated at the highest dose level (dose level 2: CCI-779 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). Patients receive 25 mg CCI-779 IV on days 1, 8, 15, and 22 and 10 mg/kg bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Overall Number of Participants Analyzed 0 0 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
40
(25 to 55)
3.Secondary Outcome
Title Clinical Best Response Rate of CCI-779 and Bevacizumab in Patients With Metastatic Renal Cell (Phase II)
Hide Description

The number of participants with clinical tumor response to treatment will be evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST).

Complete Response (CR): Disappearance of all target lesions

Partial Response (PR): At least a 30% decrease in the sum of the largest dimension (LD) of target lesions taking as reference the baseline sum LD.

Time Frame Up to 3 years from study registration
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible Phase II patients were used to assess this endpoint.
Arm/Group Title Phase II
Hide Arm/Group Description:
Phase II patients were treated at the highest dose level (dose level 2: CCI-779 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). Patients receive 25 mg CCI-779 IV on days 1, 8, 15, and 22 and 10 mg/kg bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: percentage of participants
Partial Response (PR) 20
Complete Response (CR) 0
4.Secondary Outcome
Title Time to Progression (Phase II)
Hide Description The time to progression is defined as the time from registration to the time of progression. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred. The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Time Frame Up to 3 years from study registration
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible participants in Phase II were used for this endpoint.
Arm/Group Title Phase II
Hide Arm/Group Description:
Phase II patients were treated at the highest dose level (dose level 2: CCI-779 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). Patients receive 25 mg CCI-779 IV on days 1, 8, 15, and 22 and 10 mg/kg bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Overall Number of Participants Analyzed 40
Median (95% Confidence Interval)
Unit of Measure: months
7.6
(4.0 to 7.8)
5.Secondary Outcome
Title Overall Survival (Phase I and II)
Hide Description The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Time Frame Up to 3 years from study registration
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible participants were used for this endpoint.
Arm/Group Title Phase 1, Dose Level 1 Phase I, Dose Level 2 Phase II
Hide Arm/Group Description:
Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 in escalating dose levels to determine Maximum Tolerated Dose (MTD). In the phase I portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. The first three patients began at dose level 1 and cohort doses escalate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 In the Phase 1, Dose Level 2 portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and IV Bevacizumab (level 1=10 mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Phase II patients were treated at the highest dose level (dose level 2: CCI-779 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). Patients receive 25 mg CCI-779 IV on days 1, 8, 15, and 22 and 10 mg/kg bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Overall Number of Participants Analyzed 6 6 40
Median (95% Confidence Interval)
Unit of Measure: months
24.4 [1] 
(4.6 to NA)
17
(4.4 to 54.8)
20.6
(11.5 to 23.7)
[1]
Upper 95% confidence limit wasn't calculable due to an insufficient number of events
Time Frame [Not Specified]
Adverse Event Reporting Description All patients that began study treatment and were assessed for adverse events are included in this report. Of the 46 patients that registered, one patient canceled prior to treatment and was not assessed for adverse events. Therefore, 45 patients are used in this report.
 
Arm/Group Title Phase I, Dose Level 1 Phase I, Dose Level 2 Phase II
Hide Arm/Group Description Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 In the Phase 1, Dose Level 1 portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and IV Bevacizumab (level 1=5mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15 In the Phase 1, Dose Level 2 portion, cohorts of 3-6 eligible patients were treated with CCI-779 (25 mg IV weekly) and IV Bevacizumab (level 1=5mg/kg) every other week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Phase II patients were treated at the highest dose level (dose level 2: CCI-779 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). Patients receive 25 mg CCI-779 IV on days 1, 8, 15, and 22 and 10 mg/kg bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
All-Cause Mortality
Phase I, Dose Level 1 Phase I, Dose Level 2 Phase II
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Phase I, Dose Level 1 Phase I, Dose Level 2 Phase II
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/8 (37.50%)      2/6 (33.33%)      12/45 (26.67%)    
Blood and lymphatic system disorders       
Hemoglobin decreased  1  1/8 (12.50%)  2 0/6 (0.00%)  0 2/45 (4.44%)  2
Cardiac disorders       
Left ventricular failure  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Palpitations  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Gastrointestinal disorders       
Abdominal pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2
Anal fistula  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Ascites  1  1/8 (12.50%)  2 0/6 (0.00%)  0 0/45 (0.00%)  0
Constipation  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Dyspepsia  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Gastric perforation  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Gastrointestinal disorder  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Jejunal perforation  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Lower gastrointestinal hemorrhage  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Nausea  1  1/8 (12.50%)  1 1/6 (16.67%)  1 0/45 (0.00%)  0
Peritoneal hemorrhage  1  1/8 (12.50%)  2 0/6 (0.00%)  0 0/45 (0.00%)  0
Vomiting  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
General disorders       
Chest pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Fatigue  1  1/8 (12.50%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1
Injection site reaction  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Infections and infestations       
Pneumonia  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Injury, poisoning and procedural complications       
Wound dehiscence  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Investigations       
Activated partial thromboplastin time prolonged  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Creatinine increased  1  1/8 (12.50%)  1 1/6 (16.67%)  1 0/45 (0.00%)  0
INR increased  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Lymphocyte count decreased  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Metabolism and nutrition disorders       
Anorexia  1  0/8 (0.00%)  0 2/6 (33.33%)  2 0/45 (0.00%)  0
Dehydration  1  2/8 (25.00%)  2 1/6 (16.67%)  1 0/45 (0.00%)  0
Serum calcium decreased  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Serum phosphate decreased  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Serum sodium decreased  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Musculoskeletal and connective tissue disorders       
Neck pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Nervous system disorders       
Depressed level of consciousness  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Headache  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Peripheral motor neuropathy  1  0/8 (0.00%)  0 1/6 (16.67%)  1 1/45 (2.22%)  1
Speech disorder  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Psychiatric disorders       
Confusion  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Renal and urinary disorders       
Renal failure  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Dyspnea  1  1/8 (12.50%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1
Epistaxis  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Pleural effusion  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Skin and subcutaneous tissue disorders       
Skin disorder  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Vascular disorders       
Thrombosis  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 6
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase I, Dose Level 1 Phase I, Dose Level 2 Phase II
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/8 (100.00%)      6/6 (100.00%)      45/45 (100.00%)    
Blood and lymphatic system disorders       
Hemoglobin decreased  1  7/8 (87.50%)  23 6/6 (100.00%)  25 40/45 (88.89%)  161
Hemolysis  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Lymphatic disorder  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Cardiac disorders       
Cardiac pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2
Palpitations  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Ventricular arrhythmia  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Endocrine disorders       
Hyperthyroidism  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Eye disorders       
Dry eye syndrome  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  4
Gastrointestinal disorders       
Abdominal distension  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  3
Abdominal pain  1  1/8 (12.50%)  3 1/6 (16.67%)  3 4/45 (8.89%)  5
Anal exam abnormal  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Anal mucositis  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Ascites  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  3
Constipation  1  1/8 (12.50%)  2 1/6 (16.67%)  1 4/45 (8.89%)  6
Diarrhea  1  3/8 (37.50%)  13 5/6 (83.33%)  13 18/45 (40.00%)  54
Dyspepsia  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Dysphagia  1  1/8 (12.50%)  2 1/6 (16.67%)  2 1/45 (2.22%)  1
Ear, nose and throat examination abnormal  1  0/8 (0.00%)  0 1/6 (16.67%)  2 7/45 (15.56%)  9
Flatulence  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Gastritis  1  0/8 (0.00%)  0 1/6 (16.67%)  3 0/45 (0.00%)  0
Gastrointestinal disorder  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2
Gingival pain  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Hemorrhoids  1  1/8 (12.50%)  2 0/6 (0.00%)  0 1/45 (2.22%)  1
Ileus  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Lower gastrointestinal hemorrhage  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2
Mucositis oral  1  2/8 (25.00%)  10 4/6 (66.67%)  9 26/45 (57.78%)  73
Nausea  1  2/8 (25.00%)  3 3/6 (50.00%)  5 10/45 (22.22%)  21
Oesophagoscopy abnormal  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Oral pain  1  1/8 (12.50%)  1 0/6 (0.00%)  0 2/45 (4.44%)  4
Proctitis  1  1/8 (12.50%)  2 0/6 (0.00%)  0 0/45 (0.00%)  0
Proctoscopy abnormal  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Rectal hemorrhage  1  1/8 (12.50%)  2 0/6 (0.00%)  0 0/45 (0.00%)  0
Tooth development disorder  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Toothache  1  0/8 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  5
Upper gastrointestinal hemorrhage  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Vomiting  1  1/8 (12.50%)  1 3/6 (50.00%)  4 3/45 (6.67%)  5
General disorders       
Chest pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Chills  1  1/8 (12.50%)  1 0/6 (0.00%)  0 3/45 (6.67%)  6
Edema limbs  1  0/8 (0.00%)  0 1/6 (16.67%)  3 5/45 (11.11%)  7
Facial pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Fatigue  1  2/8 (25.00%)  6 5/6 (83.33%)  23 35/45 (77.78%)  171
Fever  1  0/8 (0.00%)  0 1/6 (16.67%)  1 4/45 (8.89%)  5
Localized edema  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Pain  1  1/8 (12.50%)  1 0/6 (0.00%)  0 5/45 (11.11%)  7
Immune system disorders       
Hypersensitivity  1  0/8 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  3
Infections and infestations       
Bladder infection  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Infection  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Mucosal infection  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Otitis media  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Pneumonia  1  1/8 (12.50%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1
Sinusitis  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  3
Tooth infection  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Urinary tract infection  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2
Injury, poisoning and procedural complications       
Fracture  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Wound dehiscence  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Investigations       
Activated partial thromboplastin time prolonged  1  1/8 (12.50%)  1 1/6 (16.67%)  2 0/45 (0.00%)  0
Alanine aminotransferase increased  1  0/8 (0.00%)  0 1/6 (16.67%)  1 7/45 (15.56%)  16
Alkaline phosphatase increased  1  0/8 (0.00%)  0 1/6 (16.67%)  7 10/45 (22.22%)  24
Amylase increased  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Aspartate aminotransferase increased  1  2/8 (25.00%)  2 1/6 (16.67%)  1 11/45 (24.44%)  25
Blood bilirubin increased  1  0/8 (0.00%)  0 1/6 (16.67%)  1 1/45 (2.22%)  2
Creatinine increased  1  5/8 (62.50%)  22 3/6 (50.00%)  7 26/45 (57.78%)  145
INR increased  1  0/8 (0.00%)  0 1/6 (16.67%)  2 0/45 (0.00%)  0
Laboratory test abnormal  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Leukocyte count decreased  1  0/8 (0.00%)  0 1/6 (16.67%)  1 3/45 (6.67%)  10
Lipase increased  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Lymphocyte count decreased  1  2/8 (25.00%)  9 2/6 (33.33%)  3 1/45 (2.22%)  2
Neutrophil count decreased  1  3/8 (37.50%)  5 3/6 (50.00%)  5 3/45 (6.67%)  6
Platelet count decreased  1  3/8 (37.50%)  7 4/6 (66.67%)  16 19/45 (42.22%)  57
Serum cholesterol increased  1  3/8 (37.50%)  25 6/6 (100.00%)  20 31/45 (68.89%)  115
Weight gain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Weight loss  1  0/8 (0.00%)  0 1/6 (16.67%)  9 10/45 (22.22%)  29
Metabolism and nutrition disorders       
Alkalosis  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Anorexia  1  2/8 (25.00%)  4 5/6 (83.33%)  23 18/45 (40.00%)  47
Blood bicarbonate decreased  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Blood glucose increased  1  1/8 (12.50%)  1 2/6 (33.33%)  3 14/45 (31.11%)  56
Blood uric acid increased  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Dehydration  1  0/8 (0.00%)  0 0/6 (0.00%)  0 5/45 (11.11%)  6
Serum albumin decreased  1  1/8 (12.50%)  1 1/6 (16.67%)  1 4/45 (8.89%)  18
Serum calcium decreased  1  2/8 (25.00%)  2 4/6 (66.67%)  7 11/45 (24.44%)  20
Serum calcium increased  1  2/8 (25.00%)  2 2/6 (33.33%)  2 4/45 (8.89%)  7
Serum magnesium increased  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Serum phosphate decreased  1  3/8 (37.50%)  8 1/6 (16.67%)  2 10/45 (22.22%)  14
Serum potassium decreased  1  0/8 (0.00%)  0 2/6 (33.33%)  3 3/45 (6.67%)  6
Serum potassium increased  1  0/8 (0.00%)  0 1/6 (16.67%)  1 2/45 (4.44%)  5
Serum sodium decreased  1  1/8 (12.50%)  1 2/6 (33.33%)  2 2/45 (4.44%)  13
Serum sodium increased  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Serum triglycerides increased  1  3/8 (37.50%)  14 3/6 (50.00%)  16 33/45 (73.33%)  132
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/8 (0.00%)  0 2/6 (33.33%)  3 1/45 (2.22%)  2
Back pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Bone pain  1  0/8 (0.00%)  0 1/6 (16.67%)  1 3/45 (6.67%)  8
Chest wall pain  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Muscle weakness  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Muscle weakness trunk  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Myalgia  1  0/8 (0.00%)  0 1/6 (16.67%)  3 2/45 (4.44%)  2
Neck pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Pain in extremity  1  0/8 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumor pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  10
Nervous system disorders       
Dizziness  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  3
Dysgeusia  1  0/8 (0.00%)  0 1/6 (16.67%)  5 5/45 (11.11%)  15
Headache  1  2/8 (25.00%)  3 1/6 (16.67%)  2 6/45 (13.33%)  16
Intracranial hemorrhage  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Memory impairment  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  4
Neurological disorder NOS  1  0/8 (0.00%)  0 1/6 (16.67%)  1 1/45 (2.22%)  1
Peripheral motor neuropathy  1  2/8 (25.00%)  2 1/6 (16.67%)  1 3/45 (6.67%)  4
Peripheral sensory neuropathy  1  0/8 (0.00%)  0 1/6 (16.67%)  2 1/45 (2.22%)  1
Syncope  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Psychiatric disorders       
Anxiety  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  3
Confusion  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Depression  1  0/8 (0.00%)  0 1/6 (16.67%)  1 4/45 (8.89%)  5
Insomnia  1  1/8 (12.50%)  3 0/6 (0.00%)  0 5/45 (11.11%)  22
Personality change  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Renal and urinary disorders       
Bladder pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Bladder spasm  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Hemorrhage urinary tract  1  0/8 (0.00%)  0 0/6 (0.00%)  0 4/45 (8.89%)  6
Proteinuria  1  5/8 (62.50%)  20 2/6 (33.33%)  4 24/45 (53.33%)  84
Urinary frequency  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2
Urinary retention  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Respiratory, thoracic and mediastinal disorders       
Allergic rhinitis  1  2/8 (25.00%)  2 0/6 (0.00%)  0 3/45 (6.67%)  10
Atelectasis  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Cough  1  2/8 (25.00%)  5 2/6 (33.33%)  2 7/45 (15.56%)  9
Dyspnea  1  0/8 (0.00%)  0 2/6 (33.33%)  6 8/45 (17.78%)  13
Epistaxis  1  2/8 (25.00%)  10 3/6 (50.00%)  4 22/45 (48.89%)  86
Hypoxia  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Laryngeal mucositis  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Nasal congestion  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Pharyngeal examination abnormal  1  2/8 (25.00%)  2 0/6 (0.00%)  0 0/45 (0.00%)  0
Pharyngolaryngeal pain  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  3
Pneumonitis  1  0/8 (0.00%)  0 2/6 (33.33%)  2 4/45 (8.89%)  6
Respiratory disorder  1  1/8 (12.50%)  1 0/6 (0.00%)  0 1/45 (2.22%)  2
Voice alteration  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  7
Skin and subcutaneous tissue disorders       
Alopecia  1  1/8 (12.50%)  2 0/6 (0.00%)  0 5/45 (11.11%)  12
Decubitus ulcer  1  1/8 (12.50%)  1 0/6 (0.00%)  0 0/45 (0.00%)  0
Dry skin  1  1/8 (12.50%)  3 0/6 (0.00%)  0 1/45 (2.22%)  2
Hand-and-foot syndrome  1  0/8 (0.00%)  0 0/6 (0.00%)  0 6/45 (13.33%)  9
Nail disorder  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Pain of skin  1  1/8 (12.50%)  1 0/6 (0.00%)  0 1/45 (2.22%)  10
Petechiae  1  1/8 (12.50%)  1 0/6 (0.00%)  0 4/45 (8.89%)  11
Pruritus  1  0/8 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  5
Rash acneiform  1  0/8 (0.00%)  0 2/6 (33.33%)  7 7/45 (15.56%)  9
Rash desquamating  1  3/8 (37.50%)  22 3/6 (50.00%)  8 13/45 (28.89%)  43
Skin disorder  1  0/8 (0.00%)  0 1/6 (16.67%)  1 2/45 (4.44%)  3
Skin hyperpigmentation  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2
Skin ulceration  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Sweating  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  5
Vascular disorders       
Flushing  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Hematoma  1  0/8 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  3
Hemorrhage  1  1/8 (12.50%)  7 0/6 (0.00%)  0 0/45 (0.00%)  0
Hypertension  1  3/8 (37.50%)  9 2/6 (33.33%)  3 15/45 (33.33%)  75
Hypotension  1  0/8 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 6
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: Jaime Merchan, M.D.
Organization: University of Miami – Sylvester Comprehensive Cancer Center
EMail: jmerchan2@med.miami.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112840     History of Changes
Other Study ID Numbers: NCI-2009-00109
NCI-2009-00109 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000428311
NCI-6986
MC0452 ( Other Identifier: Mayo Clinic )
6986 ( Other Identifier: CTEP )
N01CM62205 ( U.S. NIH Grant/Contract )
First Submitted: June 2, 2005
First Posted: June 3, 2005
Results First Submitted: January 6, 2014
Results First Posted: September 11, 2014
Last Update Posted: November 16, 2015