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Vaccine Therapy With PROSTVAC/TRICOM and Flutamide Versus Flutamide Alone to Treat Prostate Cancer

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ClinicalTrials.gov Identifier: NCT00450463
Recruitment Status : Completed
First Posted : March 22, 2007
Results First Posted : November 26, 2018
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Ravi A. Madan, M.D., National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: Sargramostim (GM-CSF, Leukine)
Drug: Flutamide (Eulexin)
Biological: PROSTVAC-F/ TRICOM
Biological: PROSTVAC-V/TRICOM
Enrollment 64
Recruitment Details  
Pre-assignment Details Primary focus of this study compares flutamide with/without vaccine. While patients could get vaccine alone after flutamide progression, this was not a primary focus of the study. With only 11 patients, this group was an exploratory endeavor and there was no statistical plan for comparison to the primary groups.
Arm/Group Title Flutamide Alone Flutamide + Vaccine + Sargramostim
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Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.

Flutamide (Eulexin): Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.

Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.

Sargramostim (GM-CSF, Leukine): A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant DNA technology in yeast Saccharomyces cerevisiae). Sargramostim is a 127 amino acid glycoprotein, altered from the native, natural human GM-CSF molecule; the position 23 arginine has been replaced with a leucine to facilitate the expression of the protein in yeast

Period Title: Initial Drug Administration
Started 33 31
Completed 33 31
Not Completed 0 0
Period Title: Progressed to Receive Vaccine Alone
Started 11 0
Completed 11 0
Not Completed 0 0
Arm/Group Title Flutamide Alone Flutamide + Vaccine + Sargramostim Total
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Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.

Flutamide (Eulexin): Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.

Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.

Sargramostim (GM-CSF, Leukine): A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant DNA technology in yeast Saccharomyces cerevisiae). Sargramostim is a 127 amino acid glycoprotein, altered from the native, natural human GM-CSF molecule; the position 23 arginine has been replaced with a leucine to facilitate the expression of the protein in yeast

Total of all reporting groups
Overall Number of Baseline Participants 33 31 64
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 31 participants 64 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
8
  24.2%
7
  22.6%
15
  23.4%
>=65 years
25
  75.8%
24
  77.4%
49
  76.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 31 participants 64 participants
71.82  (8.61) 69.84  (8.87) 70.83  (8.74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 31 participants 64 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
33
 100.0%
31
 100.0%
64
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 31 participants 64 participants
Hispanic or Latino
2
   6.1%
1
   3.2%
3
   4.7%
Not Hispanic or Latino
31
  93.9%
30
  96.8%
61
  95.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 31 participants 64 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
  18.2%
5
  16.1%
11
  17.2%
White
27
  81.8%
26
  83.9%
53
  82.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 33 participants 31 participants 64 participants
33
 100.0%
31
 100.0%
64
 100.0%
1.Primary Outcome
Title Time to Treatment Failure
Hide Description Time to treatment failure is defined as a rising Prostatic Specific Antigen (PSA) (Bubley criteria, JCO 1999), development of metastatic disease, or removal from treatment due to excessive toxicity) compared to patients receiving flutamide alone. Normal PSA is 4.0 ng/mL or lower.
Time Frame Median Potential Follow-up of 46.7 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Although patients without radiographic progression were allowed to get vaccine after progression on flutamide, the primary comparison in the two groups of this study was Flutamide alone vs. Fluatmiade + vaccine simultaneously. Thus the data on TTF presented is for progression on flutamide alone.
Arm/Group Title Flutamide Alone Flutamide + Vaccine + Sargramostim
Hide Arm/Group Description:

Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.

Flutamide (Eulexin): Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.

Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.

Sargramostim (GM-CSF, Leukine): A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant deoxyribonucleic acid (DNA) technology in yeast Saccharomyces cerevisiae).

Overall Number of Participants Analyzed 33 31
Median (Full Range)
Unit of Measure: Months
4.5
(2 to 70)
6.9
(2.5 to 40)
2.Secondary Outcome
Title Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Hide Description Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame Median Potential Follow-up of 46.7 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Flutamide Alone Flutamide + Vaccine + Sargramostim Vaccine Alone After Flutamide
Hide Arm/Group Description:

Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.

Flutamide (Eulexin): Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.

Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.

Sargramostim (GM-CSF, Leukine): A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant deoxyribonucleic acid (DNA) technology in yeast Saccharomyces cerevisiae).

May receive vaccine treatment after flutamide is discontinued.
Overall Number of Participants Analyzed 33 31 11
Measure Type: Count of Participants
Unit of Measure: Participants
33
 100.0%
31
 100.0%
11
 100.0%
3.Secondary Outcome
Title Number of Participants With Prostatic Specific Antigen (PSA) Response
Hide Description Complete response is PSA <0.2 confirmed by a second reading at least 4 weeks later. All patients with a PSA decline of >50% (confirmed by a second value at least 4 weeks after the first) and who have no other evidence of disease progression will be reported with both PSA decline only and PSA decline and stable disease on scans. A 25% increase in PSA over nadir is progressive disease with or without evidence of metastatic disease, and/or development of disease on scans or a second occurrence of rising PSA levels in the absence of clinical progression.
Time Frame Median potential follow-up for all patients is 46.7 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Although patients without radiographic progression were allowed to get vaccine after progression on flutamide, the primary comparison in the two groups of this study was Flutamide alone vs. Fluatmiade + vaccine simultaneously.
Arm/Group Title Flutamide Alone Flutamide + Vaccine + Sargramostim
Hide Arm/Group Description:

Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.

Flutamide (Eulexin): Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.

Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.

Sargramostim (GM-CSF, Leukine): A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant deoxyribonucleic acid (DNA) technology in yeast Saccharomyces cerevisiae).

Overall Number of Participants Analyzed 33 31
Measure Type: Count of Participants
Unit of Measure: Participants
7
  21.2%
7
  22.6%
4.Secondary Outcome
Title Percentage of Participants With Antigen Specific Immune Responses Against Prostatic Specific Antigen (PSA)
Hide Description Antigen specific responses were evaluated using intracellular cytokine staining of cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) cells (evaluating cluster of Differentiation 107a (CD107a), INFg, Interleukin-2 (IL-2), and tumor necrosis factor (TNF) for CD4+ and CD8+ T-cells. Peripheral blood mononuclear cells were separated by Ficoll-Hypaque density gradient separation, washed three times, and preserved in 90% heat-inactivated human A and B blood-type antigens) AB serum and 10% Dimethyl sulfoxide (DMSO) in liquid nitrogen at a concentration of 1 × 10^7 cells/mL until assayed. Analysis of antigen-specific responses following therapy was assessed by intracellular cytokine staining following a period of in vitro stimulation with overlapping 15-mer peptide pools. A more complete description can be found at Heery CR et al, Cancer Immunol Res. 2015 Nov;3(11):1248-56.
Time Frame 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Flutamide Alone Flutamide + Vaccine + Sargramostim
Hide Arm/Group Description:

Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.

Flutamide (Eulexin): Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.

Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.S argramostim (GM-CSF, Leukine): A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant deoxyribonucleic acid (DNA) technology in yeast Saccharomyces cerevisiae). Sargramostim is a 127 amino acid glycoprotein, altered from the native, natural human GM-CSF molecule; the position 23 arginine has been replaced with a leucine to facilitate the expression
Overall Number of Participants Analyzed 19 18
Measure Type: Number
Unit of Measure: percentage of participants
58 56
Time Frame Median Potential Follow-up of 46.7 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Flutamide Alone Flutamide + Vaccine + Sargramostim Vaccine Alone After Flutamide
Hide Arm/Group Description

Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.

Flutamide (Eulexin): Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.

Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.

Sargramostim (GM-CSF, Leukine): A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant DNA technology in yeast Saccharomyces cerevisiae). Sargramostim is a 127 amino acid glycoprotein, altered from the native, natural human GM-CSF molecule; the position 23 arginine has been replaced with a leucine to facilitate the expression of the protein in yeast

May receive vaccine treatment after flutamide is discontinued.
All-Cause Mortality
Flutamide Alone Flutamide + Vaccine + Sargramostim Vaccine Alone After Flutamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/33 (0.00%)      0/31 (0.00%)      0/11 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Flutamide Alone Flutamide + Vaccine + Sargramostim Vaccine Alone After Flutamide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/33 (12.12%)      5/31 (16.13%)      0/11 (0.00%)    
Cardiac disorders       
Aortic valve disease  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Cardiac disorders - Other, valvular heart disease  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Mitral valve disease  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Palpitations  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Pulmonary valve disease  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Sinus tachycardia  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Immune system disorders       
Anaphylaxis  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Infections and infestations       
Urinary tract infection  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Wound infection  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Injury, poisoning and procedural complications       
Ankle fracture  1  1/33 (3.03%)  2 0/31 (0.00%)  0 0/11 (0.00%)  0
Investigations       
Creatinine increased  1  1/33 (3.03%)  2 1/31 (3.23%)  1 0/11 (0.00%)  0
Metabolism and nutrition disorders       
Hyperglycemia  1  0/33 (0.00%)  0 1/31 (3.23%)  7 0/11 (0.00%)  0
Nervous system disorders       
Dizziness  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Transient ischemic attacks  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Renal and urinary disorders       
Hematuria  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Renal and urinary disorders - Other, hydronephrosis  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Urinary tract obstruction  1  1/33 (3.03%)  1 1/31 (3.23%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Dyspnea  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Pulmonary hypertension  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Vascular disorders       
Hypertension  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Thromboembolic event  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Flutamide Alone Flutamide + Vaccine + Sargramostim Vaccine Alone After Flutamide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/33 (96.97%)      29/31 (93.55%)      11/11 (100.00%)    
Blood and lymphatic system disorders       
Anemia  1  13/33 (39.39%)  28 14/31 (45.16%)  25 0/11 (0.00%)  0
Blood and lymphatic system disorders - Other, eosinophilia  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Cardiac disorders       
Aortic valve disease  1  1/33 (3.03%)  2 1/31 (3.23%)  1 0/11 (0.00%)  0
Atrial fibrillation  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Cardiac disorders - Other, specify  1 [1]  3/33 (9.09%)  3 0/31 (0.00%)  0 0/11 (0.00%)  0
Chest pain - cardiac  1  1/33 (3.03%)  1 1/31 (3.23%)  1 0/11 (0.00%)  0
Mitral valve disease  1  1/33 (3.03%)  1 1/31 (3.23%)  1 0/11 (0.00%)  0
Palpitations  1  1/33 (3.03%)  1 1/31 (3.23%)  1 0/11 (0.00%)  0
Pulmonary valve disease  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Sinus bradycardia  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Sinus tachycardia  1  2/33 (6.06%)  2 2/31 (6.45%)  5 0/11 (0.00%)  0
Supraventricular tachycardia  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Ventricular arrhythmia  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Cardiac disorders - Other, specify  1 [2]  0/33 (0.00%)  0 2/31 (6.45%)  3 0/11 (0.00%)  0
Ear and labyrinth disorders       
Ear and labyrinth disorders - Other, decreased hearing  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Eye disorders       
Blurred vision  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Cataract  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Conjunctivitis  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Eye disorders - Other, cataract  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Eye disorders - Other, ocular/visual floaters  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Gastrointestinal disorders       
Abdominal distension  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Constipation  1  5/33 (15.15%)  6 3/31 (9.68%)  3 1/11 (9.09%)  2
Diarrhea  1  7/33 (21.21%)  12 6/31 (19.35%)  14 0/11 (0.00%)  0
Dry mouth  1  1/33 (3.03%)  1 1/31 (3.23%)  1 1/11 (9.09%)  1
Dyspepsia  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Flatulence  1  2/33 (6.06%)  2 2/31 (6.45%)  2 0/11 (0.00%)  0
Gastroesophageal reflux disease  1  2/33 (6.06%)  2 0/31 (0.00%)  0 0/11 (0.00%)  0
Gastrointestinal disorders - Other, GI disorder, colon polyps  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Hemorrhoidal hemorrhage  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Hemorrhoids  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Nausea  1  5/33 (15.15%)  6 2/31 (6.45%)  2 0/11 (0.00%)  0
Vomiting  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
General disorders       
Chills  1  0/33 (0.00%)  0 2/31 (6.45%)  2 0/11 (0.00%)  0
Edema limbs  1  3/33 (9.09%)  4 3/31 (9.68%)  4 2/11 (18.18%)  2
Fever  1  0/33 (0.00%)  0 1/31 (3.23%)  4 0/11 (0.00%)  0
Fatigue  1  12/33 (36.36%)  13 16/31 (51.61%)  31 0/11 (0.00%)  0
Flu like symptoms  1  3/33 (9.09%)  4 10/31 (32.26%)  16 3/11 (27.27%)  4
Injection site reaction  1  11/33 (33.33%)  51 23/31 (74.19%)  175 11/11 (100.00%)  51
Pain  1  4/33 (12.12%)  6 6/31 (19.35%)  9 0/11 (0.00%)  0
Immune system disorders       
Allergic reaction  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Infections and infestations       
Bone infection  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Bronchial infection  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Infections and infestations - Other, cystitis  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Mucosal infection  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Pharyngitis  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Rhinitis infective  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Skin infection  1  0/33 (0.00%)  0 2/31 (6.45%)  2 0/11 (0.00%)  0
Soft tissue infection  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Tooth infection  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Upper respiratory infection  1  1/33 (3.03%)  2 3/31 (9.68%)  5 0/11 (0.00%)  0
Urinary tract infection  1  1/33 (3.03%)  1 1/31 (3.23%)  1 1/11 (9.09%)  1
Injury, poisoning and procedural complications       
Bruising  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Fall  1  2/33 (6.06%)  4 0/31 (0.00%)  0 0/11 (0.00%)  0
Fracture  1  3/33 (9.09%)  4 0/31 (0.00%)  0 1/11 (9.09%)  1
Investigations       
Alanine aminotransferase increased  1  10/33 (30.30%)  17 14/31 (45.16%)  26 0/11 (0.00%)  0
Alkaline phosphatase increased  1  2/33 (6.06%)  2 2/31 (6.45%)  5 1/11 (9.09%)  1
Aspartate aminotransferase increased  1  9/33 (27.27%)  11 11/31 (35.48%)  15 0/11 (0.00%)  0
Blood bilirubin increased  1  3/33 (9.09%)  3 0/31 (0.00%)  0 1/11 (9.09%)  1
CD4 lymphocytes decreased  1  6/33 (18.18%)  17 3/31 (9.68%)  7 2/11 (18.18%)  2
CPK increased  1  0/33 (0.00%)  0 2/31 (6.45%)  2 0/11 (0.00%)  0
Creatinine increased  1  9/33 (27.27%)  22 9/31 (29.03%)  13 2/11 (18.18%)  2
Investigations - Other, Bicarbonate, serum-low  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Lymphocyte count decreased  1  14/33 (42.42%)  49 15/31 (48.39%)  36 5/11 (45.45%)  10
Neutrophil count decreased  1  2/33 (6.06%)  6 1/31 (3.23%)  1 1/11 (9.09%)  1
Platelet count decreased  1  3/33 (9.09%)  9 6/31 (19.35%)  12 1/11 (9.09%)  1
Weight loss  1  1/33 (3.03%)  1 1/31 (3.23%)  1 0/11 (0.00%)  0
White blood cell decreased  1  9/33 (27.27%)  22 13/31 (41.94%)  25 2/11 (18.18%)  6
Metabolism and nutrition disorders       
Anorexia  1  3/33 (9.09%)  4 0/31 (0.00%)  0 1/11 (9.09%)  1
Dehydration  1  1/33 (3.03%)  1 1/31 (3.23%)  1 0/11 (0.00%)  0
Hypercalcemia  1  4/33 (12.12%)  8 4/31 (12.90%)  7 2/11 (18.18%)  2
Hyperglycemia  1  15/33 (45.45%)  30 17/31 (54.84%)  34 0/11 (0.00%)  0
Hyperkalemia  1  6/33 (18.18%)  11 12/31 (38.71%)  20 2/11 (18.18%)  3
Hypermagnesemia  1  1/33 (3.03%)  3 3/31 (9.68%)  4 1/11 (9.09%)  1
Hypernatremia  1  6/33 (18.18%)  14 7/31 (22.58%)  9 0/11 (0.00%)  0
Hypoalbuminemia  1  7/33 (21.21%)  13 6/31 (19.35%)  9 3/11 (27.27%)  3
Hypocalcemia  1  0/33 (0.00%)  0 2/31 (6.45%)  2 0/11 (0.00%)  0
Hypoglycemia  1  2/33 (6.06%)  3 3/31 (9.68%)  4 2/11 (18.18%)  2
Hypokalemia  1  1/33 (3.03%)  1 2/31 (6.45%)  2 0/11 (0.00%)  0
Hypomagnesemia  1  5/33 (15.15%)  6 5/31 (16.13%)  11 0/11 (0.00%)  0
Hyponatremia  1  2/33 (6.06%)  3 6/31 (19.35%)  15 2/11 (18.18%)  2
Hypophosphatemia  1  4/33 (12.12%)  12 5/31 (16.13%)  13 1/11 (9.09%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  3/33 (9.09%)  3 1/31 (3.23%)  1 0/11 (0.00%)  0
Arthritis  1  1/33 (3.03%)  1 2/31 (6.45%)  4 0/11 (0.00%)  0
Back pain  1  4/33 (12.12%)  5 4/31 (12.90%)  5 1/11 (9.09%)  1
Bone pain  1  3/33 (9.09%)  4 1/31 (3.23%)  2 1/11 (9.09%)  1
Chest wall pain  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Flank pain  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Muscle weakness lower limb  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Musculoskeletal and connective tissue disorder - Other, specify  1 [3]  1/33 (3.03%)  1 0/31 (0.00%)  0 1/11 (9.09%)  1
Myalgia  1  1/33 (3.03%)  2 4/31 (12.90%)  4 0/11 (0.00%)  0
Pain in extremity  1  5/33 (15.15%)  7 5/31 (16.13%)  6 0/11 (0.00%)  0
Trismus  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Nervous system disorders       
Dizziness  1  4/33 (12.12%)  7 3/31 (9.68%)  3 1/11 (9.09%)  1
Dysgeusia  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Headache  1  3/33 (9.09%)  5 2/31 (6.45%)  3 1/11 (9.09%)  2
Memory impairment  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Paresthesia  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Peripheral sensory neuropathy  1  1/33 (3.03%)  1 1/31 (3.23%)  1 0/11 (0.00%)  0
Syncope  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Psychiatric disorders       
Depression  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Insomnia  1  1/33 (3.03%)  1 1/31 (3.23%)  1 0/11 (0.00%)  0
Renal and urinary disorders       
Cystitis noninfective  1  1/33 (3.03%)  1 0/31 (0.00%)  0 1/11 (9.09%)  1
Hematuria  1  4/33 (12.12%)  4 6/31 (19.35%)  9 1/11 (9.09%)  1
Hemoglobinuria  1  4/33 (12.12%)  4 2/31 (6.45%)  2 3/11 (27.27%)  3
Proteinuria  1  8/33 (24.24%)  18 9/31 (29.03%)  17 1/11 (9.09%)  1
Renal and urinary disorders - Other, URI  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Urinary frequency  1  3/33 (9.09%)  3 4/31 (12.90%)  5 0/11 (0.00%)  0
Urinary incontinence  1  0/33 (0.00%)  0 2/31 (6.45%)  2 0/11 (0.00%)  0
Urinary retention  1  2/33 (6.06%)  4 1/31 (3.23%)  1 0/11 (0.00%)  0
Urinary tract obstruction  1  0/33 (0.00%)  0 1/31 (3.23%)  1 1/11 (9.09%)  1
Urinary tract pain  1  0/33 (0.00%)  0 2/31 (6.45%)  2 0/11 (0.00%)  0
Urine discoloration  1  4/33 (12.12%)  4 2/31 (6.45%)  3 0/11 (0.00%)  0
Renal and urinary disorders - Other  1  0/33 (0.00%)  0 2/31 (6.45%)  2 0/11 (0.00%)  0
Reproductive system and breast disorders       
Gynecomastia  1  1/33 (3.03%)  1 2/31 (6.45%)  2 0/11 (0.00%)  0
Testicular pain  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Allergic rhinitis  1  2/33 (6.06%)  2 2/31 (6.45%)  3 0/11 (0.00%)  0
Cough  1  4/33 (12.12%)  7 5/31 (16.13%)  6 0/11 (0.00%)  0
Dyspnea  1  3/33 (9.09%)  3 4/31 (12.90%)  6 1/11 (9.09%)  1
Nasal congestion  1  4/33 (12.12%)  6 3/31 (9.68%)  3 0/11 (0.00%)  0
Pleural effusion  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Postnasal drip  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders - Other, specify  1 [4]  0/33 (0.00%)  0 2/31 (6.45%)  2 0/11 (0.00%)  0
Sinus disorder  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Sleep apnea  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Sore throat  1  0/33 (0.00%)  0 3/31 (9.68%)  3 0/11 (0.00%)  0
Skin and subcutaneous tissue disorders       
Bullous dermatitis  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Dry skin  1  2/33 (6.06%)  2 0/31 (0.00%)  0 0/11 (0.00%)  0
Pruritus  1  1/33 (3.03%)  1 2/31 (6.45%)  2 0/11 (0.00%)  0
Rash acneiform  1  1/33 (3.03%)  2 1/31 (3.23%)  1 0/11 (0.00%)  0
Rash maculo-papular  1  1/33 (3.03%)  1 1/31 (3.23%)  1 0/11 (0.00%)  0
Skin and subcutaneous tissue disorders - Other, specify  1 [5]  3/33 (9.09%)  4 0/31 (0.00%)  0 2/11 (18.18%)  2
Skin induration  1  1/33 (3.03%)  1 1/31 (3.23%)  1 1/11 (9.09%)  1
Skin ulceration  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Skin and subcutaneous tissue disorders - Other, specify  1 [6]  0/33 (0.00%)  0 3/31 (9.68%)  4 0/11 (0.00%)  0
Surgical and medical procedures       
Surgical and medical procedures - Other, specify  1 [7]  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Surgical and medical procedures - Other, specify  1 [8]  2/33 (6.06%)  2 0/31 (0.00%)  0 0/11 (0.00%)  0
Vascular disorders       
Flushing  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
Hot flashes  1  5/33 (15.15%)  5 2/31 (6.45%)  2 0/11 (0.00%)  0
Hypertension  1  1/33 (3.03%)  2 0/31 (0.00%)  0 1/11 (9.09%)  2
Hypotension  1  1/33 (3.03%)  1 0/31 (0.00%)  0 0/11 (0.00%)  0
Thromboembolic event  1  0/33 (0.00%)  0 1/31 (3.23%)  1 0/11 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
Lt atrial enlargement; Tachypnea; Coronary disease
[2]
CAD; Tachypnea; Valvular heart disease
[3]
Muscle twitching
[4]
Congestion
[5]
Brittle nails; dermatology/skin- other: cellulitis; dry skin; well differentiated squamous cell carcinoma
[6]
Erythema left groin; scalp abrasion; lesion, right side of face; right wrist erythema
[7]
Urethral meatus dilatation surgery
[8]
Carotid endartectomy cystoscopy, biopsy
Eleven patient cross-over group have no statistical plan in the protocol for analysis, highlighting their exploratory nature.
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Name/Title: Dr. Ravi Madan
Organization: National Cancer Institute
Phone: 301-480-7168
Responsible Party: Ravi A. Madan, M.D., National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00450463     History of Changes
Other Study ID Numbers: 070107
07-C-0107
First Submitted: March 20, 2007
First Posted: March 22, 2007
Results First Submitted: June 19, 2018
Results First Posted: November 26, 2018
Last Update Posted: November 29, 2018