Trial Outcomes & Findings for ABT-751 in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy (NCT NCT00471718)
NCT ID: NCT00471718
Last Updated: 2012-07-11
Results Overview
MTD is determined by the 3+3 study design, in which patients are enrolled in cohorts of 3. In any dose cohort, if 1 patient of 3 experience dose-limiting toxicity (DLT), three additional patients will be enrolled at the same dose level. Whenever \>=2 of 6 subjects experience a DLT, then the maximum tolerated dose (MTD) has been exceeded. The MTD is generally one dose below that at which DLT occurs in \>= 2 of 6 subjects in any given cohort.
TERMINATED
PHASE1/PHASE2
27 participants
up to four weeks
2012-07-11
Participant Flow
This study began enrolling October 2004 through December 2007.
A total of 34 patients were consented in Phase I and Phase II, 7 of which were not eligible.
Participant milestones
| Measure |
Phase I/II: ABT-751
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Overall Study
STARTED
|
27
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
27
|
Reasons for withdrawal
| Measure |
Phase I/II: ABT-751
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
other complicating disease
|
1
|
|
Overall Study
disease progression
|
22
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
ABT-751 in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy
Baseline characteristics by cohort
| Measure |
Phase I/II: ABT-751
n=27 Participants
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
|
Age Continuous
|
65 years
STANDARD_DEVIATION 1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to four weeksPopulation: Phase I patients who received treatment
MTD is determined by the 3+3 study design, in which patients are enrolled in cohorts of 3. In any dose cohort, if 1 patient of 3 experience dose-limiting toxicity (DLT), three additional patients will be enrolled at the same dose level. Whenever \>=2 of 6 subjects experience a DLT, then the maximum tolerated dose (MTD) has been exceeded. The MTD is generally one dose below that at which DLT occurs in \>= 2 of 6 subjects in any given cohort.
Outcome measures
| Measure |
ABT-751
n=17 Participants
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Maximum Tolerated Dose (MTD)
|
125 mg twice a day
|
PRIMARY outcome
Timeframe: after four weeksPopulation: Men with non-measurable disease: all other lesions, bone lesions, leptomeningeal disease, cystic lesions, abdominal masses that are not followed by imaging techniques
Patients with a minimum 50% decline in PSA from pre-treatment baseline, confirmed by a second PSA 4 or more weeks later, measured in nanograms per milliliter of blood.
Outcome measures
| Measure |
ABT-751
n=19 Participants
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Number of Patients Who Demonstrated Treatment Effectiveness Based on Prostate Specific Antigen (PSA) Response in Non-measurable Disease
|
0 participants
|
SECONDARY outcome
Timeframe: after four weeksPopulation: Participants with measurable disease who completed at least one cycle of treatment with tumor assessment.
Number of participants in each best tumor response category, RECIST criteria (v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in sum longest diameter (LD) of target lesions, progressive disease (PD) \> 20% increase in sum LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of smallest sum of the LD of target lesions.
Outcome measures
| Measure |
ABT-751
n=6 Participants
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Number of Patients With Objective Response (CR & PR) by RECIST
Complete Response
|
0 participants
|
|
Number of Patients With Objective Response (CR & PR) by RECIST
Partial Response
|
0 participants
|
SECONDARY outcome
Timeframe: date on study to date of progressionPopulation: Patients who received treatment and who were available for measurement of tumor or who available for PSA testing
Number of weeks from the date the patient started study drug to the date of the patient's tumor progression documented radiographically or by PSA testing. Tumor progression is measured at baseline and after two 28-day cycles
Outcome measures
| Measure |
ABT-751
n=19 Participants
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Median Time to Tumor Progression
|
4 Weeks
Interval 3.83 to 4.17
|
SECONDARY outcome
Timeframe: date on study to date of death from any causePopulation: At the time of this analysis, all 27 patients were deceased due to progressive prostate cancer.
Number of weeks from the date the patient started study drug to the date of the patient's death.
Outcome measures
| Measure |
ABT-751
n=19 Participants
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Overall Survival
|
35.3 Weeks
Interval 26.4 to 44.2
|
SECONDARY outcome
Timeframe: at 30 days after final treatment doseNot all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening or disabling, grade 5 = death)following NCI Common Toxicity Criteria
Outcome measures
| Measure |
ABT-751
n=27 Participants
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Safety Profile Based on Number of Patients With Worst Grade Toxicities
No. of patients with worst-grade toxicity of 2
|
10 patients
|
|
Safety Profile Based on Number of Patients With Worst Grade Toxicities
No. of patients with worst-grade toxicity of 3
|
14 patients
|
|
Safety Profile Based on Number of Patients With Worst Grade Toxicities
No. of patients with worst-grade toxicity of 1
|
0 patients
|
|
Safety Profile Based on Number of Patients With Worst Grade Toxicities
No. of patients with worst-grade toxicity of 4
|
3 patients
|
|
Safety Profile Based on Number of Patients With Worst Grade Toxicities
No. of patients with worst-grade toxicity of 5
|
0 patients
|
Adverse Events
Phase I/II: ABT-751
Serious adverse events
| Measure |
Phase I/II: ABT-751
n=27 participants at risk
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
Gastrointestinal disorders
Fecal incontinence
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
back pain
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
extremity pain
|
3.7%
1/27 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
pain, tumor
|
3.7%
1/27 • Number of events 1
|
|
Blood and lymphatic system disorders
hemoglobin
|
7.4%
2/27 • Number of events 2
|
|
Psychiatric disorders
mood alteration
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
dehydration
|
7.4%
2/27 • Number of events 2
|
|
Gastrointestinal disorders
nausea
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
vomiting
|
3.7%
1/27 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
hyperglycemia
|
3.7%
1/27 • Number of events 1
|
|
Psychiatric disorders
confusion
|
7.4%
2/27 • Number of events 2
|
|
Nervous system disorders
neuropathy cranial
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
neuropathy motor weakness
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
speech impairment
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
extrapyramidal
|
3.7%
1/27 • Number of events 1
|
|
General disorders
fever
|
3.7%
1/27 • Number of events 1
|
|
Infections and infestations
Infection with normal ANC
|
3.7%
1/27 • Number of events 1
|
|
Psychiatric disorders
memory impairment
|
3.7%
1/27 • Number of events 1
|
Other adverse events
| Measure |
Phase I/II: ABT-751
n=27 participants at risk
Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 at 125mg twice daily, 7 days on, 7 days off (x2)for a 28-day cycle
|
|---|---|
|
General disorders
Constipation
|
55.6%
15/27 • Number of events 26
|
|
Nervous system disorders
neuropathy
|
48.1%
13/27 • Number of events 21
|
|
General disorders
pain
|
66.7%
18/27 • Number of events 36
|
|
Blood and lymphatic system disorders
anemia
|
66.7%
18/27 • Number of events 26
|
|
Metabolism and nutrition disorders
hyperglycemia
|
55.6%
15/27 • Number of events 21
|
|
Gastrointestinal disorders
gastrointestinal disorders
|
40.7%
11/27 • Number of events 16
|
|
General disorders
fatigue
|
70.4%
19/27 • Number of events 35
|
|
Psychiatric disorders
anorexia
|
33.3%
9/27 • Number of events 18
|
|
Gastrointestinal disorders
diarrhea
|
29.6%
8/27 • Number of events 10
|
|
Investigations
alkaline phosphatase increase
|
29.6%
8/27 • Number of events 13
|
|
Psychiatric disorders
depression
|
7.4%
2/27 • Number of events 4
|
|
Psychiatric disorders
confusion
|
11.1%
3/27 • Number of events 4
|
|
Metabolism and nutrition disorders
dehydration
|
18.5%
5/27 • Number of events 12
|
|
Metabolism and nutrition disorders
hypokalemia
|
11.1%
3/27 • Number of events 4
|
|
General disorders
fever
|
18.5%
5/27 • Number of events 6
|
|
Infections and infestations
infection
|
25.9%
7/27 • Number of events 11
|
|
Metabolism and nutrition disorders
weight loss
|
18.5%
5/27 • Number of events 5
|
|
Vascular disorders
sweats
|
11.1%
3/27 • Number of events 5
|
|
Metabolism and nutrition disorders
hypophosphatemia
|
14.8%
4/27 • Number of events 6
|
|
Investigations
neutrophil count decreased
|
14.8%
4/27 • Number of events 6
|
|
Metabolism and nutrition disorders
hyponatremia
|
25.9%
7/27 • Number of events 7
|
|
Vascular disorders
thrombosis
|
11.1%
3/27 • Number of events 4
|
|
Metabolism and nutrition disorders
hyperuricemia
|
7.4%
2/27 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
7.4%
2/27 • Number of events 4
|
|
Vascular disorders
hypertension
|
11.1%
3/27 • Number of events 9
|
|
Gastrointestinal disorders
xerostomia
|
7.4%
2/27 • Number of events 2
|
|
Metabolism and nutrition disorders
elevated transaminases
|
29.6%
8/27 • Number of events 8
|
|
Renal and urinary disorders
hematuria
|
11.1%
3/27 • Number of events 3
|
|
Renal and urinary disorders
urine retention
|
11.1%
3/27 • Number of events 3
|
|
Renal and urinary disorders
renal failure
|
7.4%
2/27 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place