Trial Outcomes & Findings for Intermittent Chemotherapy With or Without Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Metastatic Hormone Refractory Prostate Cancer (HRPC) (NCT NCT00488982)
NCT ID: NCT00488982
Last Updated: 2019-11-20
Results Overview
The Kaplan-Meier product limit method with 95% confidence intervals will be used to estimate the median time to disease progression during initial course of randomized treatment
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
125 participants
Primary outcome timeframe
Up to 7 years
Results posted on
2019-11-20
Participant Flow
Patients had to complete 6 cycles of induction chemotherapy and have a ≥ 50% decline in prostate-specific antigen to be eligible for randomization.
Participant milestones
| Measure |
Pre-Randomization
Induction chemotherapy for 6 cycles (1 cycle = 21 days)
* Docetaxel 75mg/m\^2 I.V. (intravenous) on day 2
* Prednisone 5 mg by mouth (p.o.), twice a day (b.i.d.) from day 1 to 21 (for 21 days)
|
Docetaxel and Observation
Docetaxel 75mg/m\^2 every 21 days
|
Docetaxel and GM-CSF
Docetaxel 75mg/m\^2 every 21 days and GM-CSF 250mcg/m\^2 subcutaneously days 15-28
|
|---|---|---|---|
|
Induction Chemotherapy
STARTED
|
125
|
0
|
0
|
|
Induction Chemotherapy
6 Cycles Completed
|
94
|
0
|
0
|
|
Induction Chemotherapy
≥ 50% Prostate-specific Antigen Decline
|
52
|
0
|
0
|
|
Induction Chemotherapy
COMPLETED
|
52
|
0
|
0
|
|
Induction Chemotherapy
NOT COMPLETED
|
73
|
0
|
0
|
|
Course 1
STARTED
|
0
|
25
|
27
|
|
Course 1
COMPLETED
|
0
|
13
|
13
|
|
Course 1
NOT COMPLETED
|
0
|
12
|
14
|
|
Course 2
STARTED
|
0
|
13
|
13
|
|
Course 2
COMPLETED
|
0
|
4
|
8
|
|
Course 2
NOT COMPLETED
|
0
|
9
|
5
|
|
Course 3
STARTED
|
0
|
4
|
8
|
|
Course 3
COMPLETED
|
0
|
2
|
3
|
|
Course 3
NOT COMPLETED
|
0
|
2
|
5
|
|
Response to Course 3
STARTED
|
0
|
2
|
3
|
|
Response to Course 3
COMPLETED
|
0
|
1
|
0
|
|
Response to Course 3
NOT COMPLETED
|
0
|
1
|
3
|
Reasons for withdrawal
| Measure |
Pre-Randomization
Induction chemotherapy for 6 cycles (1 cycle = 21 days)
* Docetaxel 75mg/m\^2 I.V. (intravenous) on day 2
* Prednisone 5 mg by mouth (p.o.), twice a day (b.i.d.) from day 1 to 21 (for 21 days)
|
Docetaxel and Observation
Docetaxel 75mg/m\^2 every 21 days
|
Docetaxel and GM-CSF
Docetaxel 75mg/m\^2 every 21 days and GM-CSF 250mcg/m\^2 subcutaneously days 15-28
|
|---|---|---|---|
|
Course 1
Physician Decision
|
0
|
2
|
4
|
|
Course 1
Withdrawal by Subject
|
0
|
8
|
2
|
|
Course 1
nonprotocol therapy
|
0
|
2
|
2
|
|
Course 1
Adverse Event
|
0
|
0
|
6
|
Baseline Characteristics
Intermittent Chemotherapy With or Without Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Metastatic Hormone Refractory Prostate Cancer (HRPC)
Baseline characteristics by cohort
| Measure |
All Patients Accrued
n=125 Participants
There were a total of 125 patients whom were accrued to the study and assigned to at least one course of docetaxel
|
|---|---|
|
Age, Customized
Median Age Range
|
70 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
125 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
115 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
111 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
125 participants
n=93 Participants
|
|
Gleason Score
<=6
|
22 Participants
n=93 Participants
|
|
Gleason Score
7
|
33 Participants
n=93 Participants
|
|
Gleason Score
8-10
|
70 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Up to 7 yearsThe Kaplan-Meier product limit method with 95% confidence intervals will be used to estimate the median time to disease progression during initial course of randomized treatment
Outcome measures
| Measure |
Docetaxel + Observation ON Chemotherapy
Starting Docetaxel 75mg/m2 and Observation every 21 days for at least 2 days
|
Docetaxel and GM-CSF ON Chemotherapy
Starting Docetaxel 75mg/m2 and GM-CSF 250mcg/m2 SQ days 15-28 every 28 days with at least 2 days of Docetaxel
|
Docetaxel and Observation
n=25 Participants
\- Docetaxel 75mg/m\^2 every 21 days
|
Docetaxel and GM-CSF
n=27 Participants
* Docetaxel 75mg/m\^2 every 21 days
* GM-CSF 250mcg/m2 subcutaneous (SQ) days 15-28
|
|---|---|---|---|---|
|
Time to Progression
|
—
|
—
|
1.5 months
Interval 1.5 to 2.4
|
3.3 months
Interval 2.4 to 3.5
|
SECONDARY outcome
Timeframe: Up to 7 yearsThe Kaplan-Meier product limit method will be used to estimate the median overall survival
Outcome measures
| Measure |
Docetaxel + Observation ON Chemotherapy
n=125 Participants
Starting Docetaxel 75mg/m2 and Observation every 21 days for at least 2 days
|
Docetaxel and GM-CSF ON Chemotherapy
Starting Docetaxel 75mg/m2 and GM-CSF 250mcg/m2 SQ days 15-28 every 28 days with at least 2 days of Docetaxel
|
Docetaxel and Observation
n=25 Participants
\- Docetaxel 75mg/m\^2 every 21 days
|
Docetaxel and GM-CSF
n=27 Participants
* Docetaxel 75mg/m\^2 every 21 days
* GM-CSF 250mcg/m2 subcutaneous (SQ) days 15-28
|
|---|---|---|---|---|
|
Overall Survival
|
15.6 months
Interval 13.1 to 18.8
|
—
|
14 months
Interval 10.5 to 27.6
|
28.4 months
Interval 19.2 to 34.1
|
SECONDARY outcome
Timeframe: Up to 6 yearsPopulation: Twenty-six participants total resumed a second course of the Docetaxel, and five participants went on to resume a third course of treatment.
PSA partial response is defined by at least a 50% decline from PSA value from the baseline measurement to 12 weeks of protocol therapy. The decline must be confirmed by a second PSA value obtained 4 or more weeks later For those patients whose PSA have decreased but has not reached response criteria defined above, progressive disease is defined as 25% increase over the nadir PSA value provided that the increase is at least 5ng/mL and is confirmed.
Outcome measures
| Measure |
Docetaxel + Observation ON Chemotherapy
Starting Docetaxel 75mg/m2 and Observation every 21 days for at least 2 days
|
Docetaxel and GM-CSF ON Chemotherapy
Starting Docetaxel 75mg/m2 and GM-CSF 250mcg/m2 SQ days 15-28 every 28 days with at least 2 days of Docetaxel
|
Docetaxel and Observation
n=13 Participants
\- Docetaxel 75mg/m\^2 every 21 days
|
Docetaxel and GM-CSF
n=13 Participants
* Docetaxel 75mg/m\^2 every 21 days
* GM-CSF 250mcg/m2 subcutaneous (SQ) days 15-28
|
|---|---|---|---|---|
|
Number of Participants With PSA Response to Successive Series of Chemotherapy
PSA response to Course 2 chemotherapy
|
—
|
—
|
4 Participants
|
8 Participants
|
|
Number of Participants With PSA Response to Successive Series of Chemotherapy
PSA response to Course 3 chemotherapy
|
—
|
—
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 7 yearsMedian percentage of time will be calculated to summarize the total duration of chemotherapy and amount of docetaxel/prednisone administered while the patient is on study. The same results will be tabulated for each. For the on-chemotherapy period: will be estimated from the date of starting protocol therapy; if a patient received docetaxel on day 2 of a cycle, he will be considered to have received a full 21 days on therapy. For the off-chemotherapy period: will be calculated from the date of starting the observation or GM-CSF period to the date of resuming chemotherapy
Outcome measures
| Measure |
Docetaxel + Observation ON Chemotherapy
n=25 Participants
Starting Docetaxel 75mg/m2 and Observation every 21 days for at least 2 days
|
Docetaxel and GM-CSF ON Chemotherapy
n=27 Participants
Starting Docetaxel 75mg/m2 and GM-CSF 250mcg/m2 SQ days 15-28 every 28 days with at least 2 days of Docetaxel
|
Docetaxel and Observation
n=25 Participants
\- Docetaxel 75mg/m\^2 every 21 days
|
Docetaxel and GM-CSF
n=27 Participants
* Docetaxel 75mg/m\^2 every 21 days
* GM-CSF 250mcg/m2 subcutaneous (SQ) days 15-28
|
|---|---|---|---|---|
|
Cumulative Duration of Time on and Off Docetaxel-based Therapy
|
8.3 months
Interval 3.9 to 22.8
|
7.6 months
Interval 1.9 to 19.2
|
24.7 months
Interval 0.8 to 50.8
|
30.9 months
Interval 1.7 to 77.1
|
Adverse Events
All Accrued Patients
Serious events: 20 serious events
Other events: 0 other events
Deaths: 8 deaths
Serious adverse events
| Measure |
All Accrued Patients
n=125 participants at risk
All patients were assigned to received six 21-day cycles of docetaxel 75 mg/m2 on Day 2 of each cycle and 5 mg prednisone twice a day on Days 1-21. Following six cycles of chemotherapy, eligible subjects were randomized to no maintenance therapy or to maintenance GM-CSF therapy. Patients in both groups were followed until disease progression at which time GM-CSF was discontinued and another course of docetaxel and prednisone was administered again.
|
|---|---|
|
Infections and infestations
Febrile neutropenia
|
6.4%
8/125 • Number of events 9 • Any patient receiving at least one dose of the study treatment will be included in the analyses of toxicity during the initial chemotherapy period, but patients who cancel registration before receiving any therapy will not. All grade 3-5, expected and unexpected adverse events (AEs) were collected at all study visits from time of first treatment until at least 28 days following the last dose of study drug.
Data was not collected per intervention. All patients were assigned to the same treatment of Docetaxel/Prednisone before being assigned to the subsequent therapy arms where they may have received multiple treatment courses with multiple inductions. Abnormal lab values or test results constituted AEs only if they induced clinical signs /symptoms, required therapy, or required dose modification. There were no treatment-associated deaths.
|
|
Infections and infestations
Neutropenia
|
9.6%
12/125 • Number of events 14 • Any patient receiving at least one dose of the study treatment will be included in the analyses of toxicity during the initial chemotherapy period, but patients who cancel registration before receiving any therapy will not. All grade 3-5, expected and unexpected adverse events (AEs) were collected at all study visits from time of first treatment until at least 28 days following the last dose of study drug.
Data was not collected per intervention. All patients were assigned to the same treatment of Docetaxel/Prednisone before being assigned to the subsequent therapy arms where they may have received multiple treatment courses with multiple inductions. Abnormal lab values or test results constituted AEs only if they induced clinical signs /symptoms, required therapy, or required dose modification. There were no treatment-associated deaths.
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. Rahul Aggarwal
University of California, San Francisco
Phone: (415) 353-9278
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place