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Genomic Guided Therapy With Dasatinib or Nilutamide in Metastatic Castration-Resistant Prostate Cancer (ARS)

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ClinicalTrials.gov Identifier: NCT00918385
Recruitment Status : Terminated (Permanent closure of trial to further accrual based on IDE disapproval)
First Posted : June 11, 2009
Results First Posted : October 29, 2014
Last Update Posted : October 29, 2014
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: Nilutamide
Drug: Dasatinib
Enrollment 57
Recruitment Details Accrual open from January 2009 to July 2011 in these institutions: Dana Farber Cancer Institute, Duke Cancer Institute, MD Anderson Cancer Center, Oregon Health & Science Univ, U of CA at San Francisco, U of Washington.
Pre-assignment Details 64 consented, 7 screen failures. Of the 57 who began enrollment, 2 not assigned to treatment (withdrew consent, clinically unstable), 22 QC technical failures (received dasatinib off study) and 33 assigned per protocol (15 high AR, 18 low AR), 2 progressed before treatment. 14 high AR and 17 low AR began treatment and are included in the analysis.
Arm/Group Title Arm 1=High AR Nilutamide Arm 2= Low AR Dasatinib
Hide Arm/Group Description

High Androgen Receptor (AR) activity of >= 0.50

Nilutamide: Nilutamide 150mg orally each day for 28 days per cycle. After first progression, Nilutamide 150mg orally each day in combination with Dasatinib 100mg orally each day for 28 days per cycle.

Low Androgen Receptor (AR) activity of < 0.50

Dasatinib: Dasatinib 100mg orally daily x 28 days per cycle. After first progression, Dasatinib 100mg orally each day in combination with Nilutamide 150mg orally each day for 28 days per cycle.

Period Title: Monotherapy
Started 14 17
Completed 12 [1] 11 [1]
Not Completed 2 6
Reason Not Completed
Adverse Event             1             6
Complicating illness             1             0
[1]
Completed = received treatment until first disease progression on single agent.
Period Title: Combination Nilutamide and Dasatinib
Started 12 11
Completed 6 3
Not Completed 6 8
Reason Not Completed
Adverse Event             1             1
Withdrawal by Subject             2             0
Complicating illness             1             0
Withdrawal by Subject             2             7
Arm/Group Title Arm 1=High AR Nilutamide Arm 2= Low AR Dasatinib Total
Hide Arm/Group Description

High Androgen Receptor (AR) activity of >= 0.50

Nilutamide: Nilutamide 150mg orally each day for 28 days per cycle. After first progression, Nilutamide 150mg orally each day in combination with Dasatinib 100mg orally each day for 28 days per cycle.

Low Androgen Receptor (AR) activity of < 0.50

Dasatinib: Dasatinib 100mg orally daily x 28 days per cycle. After first progression, Dasatinib 100mg orally each day in combination with Nilutamide 150mg orally each day for 28 days per cycle.

Total of all reporting groups
Overall Number of Baseline Participants 14 17 31
Hide Baseline Analysis Population Description
64 consented but 7 screen failures, so 57 enrolled. 2 never assigned to rx (withdrew consent, clinically unstable), 33 assigned by AR activity (15 high AR to nilutamide, 18 low AR to dasatinib) and 22 QC technical failures (received dasatinib). 14 of 15 high AR and 17 of 18 low AR began protocol treatment. Analyses include the 31 treated patients.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 17 participants 31 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
  42.9%
4
  23.5%
10
  32.3%
>=65 years
8
  57.1%
13
  76.5%
21
  67.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 17 participants 31 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
14
 100.0%
17
 100.0%
31
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 17 participants 31 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
1
   7.1%
2
  11.8%
3
   9.7%
White
13
  92.9%
15
  88.2%
28
  90.3%
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: Number
Unit of measure:  Participants
United States Number Analyzed 14 participants 17 participants 31 participants
14 17 31
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS is the interval from start of monotherapy until first disease progression or death, whichever occurred first.
Time Frame During monotherapy ( at least 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm 1=High AR Nilutamide Arm 2= Low AR Dasatinib
Hide Arm/Group Description:

High Androgen Receptor (AR) activity of >= 0.50

Nilutamide: Nilutamide 150mg orally each day for 28 days per cycle. After first progression, Nilutamide 150mg orally each day in combination with Dasatinib 100mg orally each day for 28 days per cycle.

Low Androgen Receptor (AR) activity of < 0.50

Dasatinib: Dasatinib 100mg orally daily x 28 days per cycle. After first progression, Dasatinib 100mg orally each day in combination with Nilutamide 150mg orally each day for 28 days per cycle.

Overall Number of Participants Analyzed 14 17
Median (90% Confidence Interval)
Unit of Measure: months
2.8
(2.7 to 4.4)
2.6
(1.1 to 3.0)
2.Secondary Outcome
Title Overall Response Rate of Men With High AR Activity
Hide Description Tumor response was based on Response Criteria in Solid Tumors (RECIST). Complete response (CR) is defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time Frame During monotherapy (at least 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
14 subjects began treatment; 13 with response documentation are included in the calculation; 1 subject was omitted because response documentation was not provided.
Arm/Group Title Arm 1=High AR Nilutamide
Hide Arm/Group Description:

High Androgen Receptor (AR) activity of >= 0.50

Nilutamide: Nilutamide 150mg orally each day for 28 days per cycle. After first progression, Nilutamide 150mg orally each day in combination with Dasatinib 100mg orally each day for 28 days per cycle.

Overall Number of Participants Analyzed 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients with CR,PR
0
(0 to 23)
3.Secondary Outcome
Title Overall Response Rate of Men With Low AR Activity
Hide Description Tumor response is based on Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time Frame During dasatinib monotherapy ( at least 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 17 subjects treated, 15 had response documentation and are included in the calculation. Two were omitted (1 because response documentation was not provided; 1 ended treatment after 2 weeks for toxicity prior to repeat scans).
Arm/Group Title Arm 2= Low AR Dasatinib
Hide Arm/Group Description:

Low Androgen Receptor (AR) activity of < 0.50

Dasatinib: Dasatinib 100mg orally daily x 28 days per cycle. After first progression, Dasatinib 100mg orally each day in combination with Nilutamide 150mg orally each day for 28 days per cycle.

Overall Number of Participants Analyzed 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients with CR,PR
0
(0 to 21)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm 1=High AR Nilutamide Arm 2= Low AR Dasatinib Combination Nilutamide and Dasatinib
Hide Arm/Group Description

High Androgen Receptor (AR) activity of >= 0.50

Nilutamide: Nilutamide 150mg orally each day for 28 days per cycle. After first progression, Nilutamide 150mg orally each day in combination with Dasatinib 100mg orally each day for 28 days per cycle.

Low Androgen Receptor (AR) activity of < 0.50

Dasatinib: Dasatinib 100mg orally daily x 28 days per cycle. After first progression, Dasatinib 100mg orally each day in combination with Nilutamide 150mg orally each day for 28 days per cycle.

[Not Specified]
All-Cause Mortality
Arm 1=High AR Nilutamide Arm 2= Low AR Dasatinib Combination Nilutamide and Dasatinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Arm 1=High AR Nilutamide Arm 2= Low AR Dasatinib Combination Nilutamide and Dasatinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/14 (100.00%)   16/17 (94.12%)   14/23 (60.87%) 
Blood and lymphatic system disorders       
Anemia  1  11/14 (78.57%)  11/17 (64.71%)  13/23 (56.52%) 
Lymph node pain  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Ear and labyrinth disorders       
Ear and labyrinth disorders - Other  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Ear pain  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Eye disorders       
Blurred vision  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Dry eye  1  0/14 (0.00%)  1/17 (5.88%)  1/23 (4.35%) 
Eye disorders - Other  1  9/14 (64.29%)  0/17 (0.00%)  5/23 (21.74%) 
Eye pain  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Extraocular muscle paresis  0/14 (0.00%)  0/17 (0.00%)  1/23 (4.35%) 
Gastrointestinal disorders       
Abdominal pain  1  2/14 (14.29%)  2/17 (11.76%)  1/23 (4.35%) 
Anal hemorrhage  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Constipation  1  4/14 (28.57%)  6/17 (35.29%)  7/23 (30.43%) 
Diarrhea  1  4/14 (28.57%)  4/17 (23.53%)  4/23 (17.39%) 
Dyspepsia  1  1/14 (7.14%)  1/17 (5.88%)  0/23 (0.00%) 
Dysphagia  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Fecal incontinence  1  2/14 (14.29%)  0/17 (0.00%)  0/23 (0.00%) 
Flatulence  1  0/14 (0.00%)  2/17 (11.76%)  1/23 (4.35%) 
Gastritis  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Gastrointestinal disorders - Other  1  1/14 (7.14%)  1/17 (5.88%)  1/23 (4.35%) 
Hemorrhoids  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Mucositis oral  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Nausea  1  10/14 (71.43%)  6/17 (35.29%)  7/23 (30.43%) 
Rectal pain  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Vomiting  1  4/14 (28.57%)  3/17 (17.65%)  2/23 (8.70%) 
Dry mouth  1  0/14 (0.00%)  0/17 (0.00%)  1/23 (4.35%) 
Lower gastrointestinal hemorrhage  0/14 (0.00%)  0/17 (0.00%)  1/23 (4.35%) 
General disorders       
Edema limbs  1  4/14 (28.57%)  4/17 (23.53%)  1/23 (4.35%) 
Edema trunk  1  1/14 (7.14%)  1/17 (5.88%)  0/23 (0.00%) 
Fatigue  1  4/14 (28.57%)  11/17 (64.71%)  10/23 (43.48%) 
Fever  1  1/14 (7.14%)  1/17 (5.88%)  0/23 (0.00%) 
Flu like symptoms  1  1/14 (7.14%)  0/17 (0.00%)  1/23 (4.35%) 
Pain  1  6/14 (42.86%)  4/17 (23.53%)  2/23 (8.70%) 
Non-cardiac chest pain  1  0/14 (0.00%)  0/17 (0.00%)  1/23 (4.35%) 
Infections and infestations       
Gum infection  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Infections and infestations - Other  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Sinusitis  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Tooth infection  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Urinary tract infection  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Rhinitis infective  1  0/14 (0.00%)  0/17 (0.00%)  1/23 (4.35%) 
Injury, poisoning and procedural complications       
Fracture  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Investigations       
Aspartate aminotransferase increased  1  1/14 (7.14%)  0/17 (0.00%)  1/23 (4.35%) 
Creatinine increased  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Neutrophil count decreased  1  0/14 (0.00%)  4/17 (23.53%)  0/23 (0.00%) 
Platelet count decreased  1  1/14 (7.14%)  3/17 (17.65%)  2/23 (8.70%) 
Weight loss  1  0/14 (0.00%)  1/17 (5.88%)  3/23 (13.04%) 
White blood cell decreased  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Electrocardiogram QT corrected interval prolonged  1  0/14 (0.00%)  0/17 (0.00%)  2/23 (8.70%) 
Metabolism and nutrition disorders       
Anorexia  1  3/14 (21.43%)  7/17 (41.18%)  6/23 (26.09%) 
Dehydration  1  1/14 (7.14%)  1/17 (5.88%)  0/23 (0.00%) 
Hyperglycemia  1  1/14 (7.14%)  1/17 (5.88%)  1/23 (4.35%) 
Hypoalbuminemia  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Hypocalcemia  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Hypokalemia  1  2/14 (14.29%)  0/17 (0.00%)  1/23 (4.35%) 
Hyponatremia  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/14 (7.14%)  0/17 (0.00%)  1/23 (4.35%) 
Back pain  1  1/14 (7.14%)  3/17 (17.65%)  4/23 (17.39%) 
Bone pain  1  3/14 (21.43%)  2/17 (11.76%)  2/23 (8.70%) 
Buttock pain  1  1/14 (7.14%)  1/17 (5.88%)  1/23 (4.35%) 
Chest wall pain  1  1/14 (7.14%)  1/17 (5.88%)  0/23 (0.00%) 
Generalized muscle weakness  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Musculoskeletal and connective tissue disorder - Other  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Myalgia  1  1/14 (7.14%)  1/17 (5.88%)  0/23 (0.00%) 
Neck pain  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Pain in extremity  1  6/14 (42.86%)  5/17 (29.41%)  4/23 (17.39%) 
Nervous system disorders       
Ataxia  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Cognitive disturbance  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Dizziness  1  3/14 (21.43%)  2/17 (11.76%)  2/23 (8.70%) 
Dysgeusia  1  0/14 (0.00%)  3/17 (17.65%)  0/23 (0.00%) 
Headache  1  2/14 (14.29%)  1/17 (5.88%)  0/23 (0.00%) 
Memory impairment  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Peripheral motor neuropathy  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Peripheral sensory neuropathy  1  2/14 (14.29%)  3/17 (17.65%)  3/23 (13.04%) 
Sinus pain  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Dysgeusia  1  0/14 (0.00%)  0/17 (0.00%)  5/23 (21.74%) 
Headache  1  0/14 (0.00%)  0/17 (0.00%)  2/23 (8.70%) 
Psychiatric disorders       
Agitation  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Anxiety  1  1/14 (7.14%)  0/17 (0.00%)  2/23 (8.70%) 
Depression  1  2/14 (14.29%)  1/17 (5.88%)  0/23 (0.00%) 
Insomnia  1  1/14 (7.14%)  2/17 (11.76%)  2/23 (8.70%) 
Renal and urinary disorders       
Hematuria  1  1/14 (7.14%)  2/17 (11.76%)  1/23 (4.35%) 
Renal and urinary disorders - Other  1  2/14 (14.29%)  1/17 (5.88%)  1/23 (4.35%) 
Urinary frequency  1  1/14 (7.14%)  1/17 (5.88%)  2/23 (8.70%) 
Urinary incontinence  1  2/14 (14.29%)  0/17 (0.00%)  0/23 (0.00%) 
Urinary retention  1  2/14 (14.29%)  0/17 (0.00%)  0/23 (0.00%) 
Urinary tract obstruction  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Urine discoloration  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Reproductive system and breast disorders       
Gynecomastia  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Pelvic pain  1  2/14 (14.29%)  2/17 (11.76%)  3/23 (13.04%) 
Scrotal pain  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Testicular pain  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Allergic rhinitis  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Cough  1  0/14 (0.00%)  1/17 (5.88%)  2/23 (8.70%) 
Dyspnea  1  0/14 (0.00%)  3/17 (17.65%)  3/23 (13.04%) 
Epistaxis  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Hiccups  1  1/14 (7.14%)  0/17 (0.00%)  2/23 (8.70%) 
Pleural effusion  1  0/14 (0.00%)  2/17 (11.76%)  0/23 (0.00%) 
Respiratory, thoracic and mediastinal disorders - Other  1  2/14 (14.29%)  1/17 (5.88%)  4/23 (17.39%) 
Sinus disorder  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Voice alteration  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Pharyngolaryngeal pain  1  0/14 (0.00%)  0/17 (0.00%)  1/23 (4.35%) 
Skin and subcutaneous tissue disorders       
Dry skin  1  0/14 (0.00%)  2/17 (11.76%)  1/23 (4.35%) 
Purpura  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Rash maculo-papular  1  3/14 (21.43%)  1/17 (5.88%)  0/23 (0.00%) 
Vascular disorders       
Hot flashes  1  4/14 (28.57%)  1/17 (5.88%)  1/23 (4.35%) 
Hypertension  1  0/14 (0.00%)  1/17 (5.88%)  0/23 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm 1=High AR Nilutamide Arm 2= Low AR Dasatinib Combination Nilutamide and Dasatinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/14 (21.43%)   1/17 (5.88%)   1/23 (4.35%) 
Blood and lymphatic system disorders       
Anemia  1  1/14 (7.14%)  1/17 (5.88%)  0/23 (0.00%) 
Eye disorders       
Eye disorders - Other  1  0/14 (0.00%)  0/17 (0.00%)  1/23 (4.35%) 
Nervous system disorders       
Dizziness  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Renal and urinary disorders       
Obstruction, GU:Ureter  1  1/14 (7.14%)  0/17 (0.00%)  0/23 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Daniel George
Organization: Duke University
Phone: (919) 668 4615
EMail: daniel.george@duke.edu
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00918385    
Other Study ID Numbers: Pro00012159
CA180-263
First Submitted: June 10, 2009
First Posted: June 11, 2009
Results First Submitted: September 11, 2014
Results First Posted: October 29, 2014
Last Update Posted: October 29, 2014