Trial Outcomes & Findings for Sirolimus Before Surgery in Treating Patients With Advanced Localized Prostate Cancer (NCT NCT00311623)
NCT ID: NCT00311623
Last Updated: 2019-02-22
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
32 participants
Primary outcome timeframe
Day 15 post-intervention
Results posted on
2019-02-22
Participant Flow
Participant milestones
| Measure |
Control Group
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Receive no intervention on Days 1-14. Surgery performed on Day 15.
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Low-dose Rapamycin (3mg)
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 3mg: Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
High-dose Rapamycin (6mg)
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 6mg: Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
20
|
2
|
|
Overall Study
COMPLETED
|
10
|
20
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
2
|
Reasons for withdrawal
| Measure |
Control Group
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Receive no intervention on Days 1-14. Surgery performed on Day 15.
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Low-dose Rapamycin (3mg)
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 3mg: Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
High-dose Rapamycin (6mg)
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 6mg: Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
|---|---|---|---|
|
Overall Study
Physician Decision
|
0
|
0
|
2
|
Baseline Characteristics
Data for PSA decline was not collected for 5 participants from the Control Arm and 3 participants from the Low-dose arm.
Baseline characteristics by cohort
| Measure |
Control Group
n=10 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Receive no intervention on Days 1-14. Surgery performed on Day 15.
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Low-dose Rapamycin (3mg)
n=20 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 3mg: Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
High-dose Rapamycin (6mg)
n=2 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 6mg: Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
|
64 years
n=10 Participants
|
61.5 years
n=20 Participants
|
57.5 years
n=2 Participants
|
62.5 years
n=32 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=32 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=10 Participants
|
20 Participants
n=20 Participants
|
2 Participants
n=2 Participants
|
32 Participants
n=32 Participants
|
|
Race/Ethnicity, Customized
non-Hispanic
|
10 Participants
n=10 Participants
|
20 Participants
n=20 Participants
|
2 Participants
n=2 Participants
|
32 Participants
n=32 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
10 Participants
n=10 Participants
|
16 Participants
n=20 Participants
|
2 Participants
n=2 Participants
|
28 Participants
n=32 Participants
|
|
Race/Ethnicity, Customized
African-American
|
0 Participants
n=10 Participants
|
4 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
4 Participants
n=32 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=10 Participants
|
20 participants
n=20 Participants
|
2 participants
n=2 Participants
|
32 participants
n=32 Participants
|
|
Body Mass Index
|
28.0 kg/m2
STANDARD_DEVIATION 2.31 • n=10 Participants
|
27.8 kg/m2
STANDARD_DEVIATION 4.95 • n=20 Participants
|
28.7 kg/m2
STANDARD_DEVIATION 1.75 • n=2 Participants
|
27.83 kg/m2
STANDARD_DEVIATION 4.09 • n=32 Participants
|
|
Biopsy Gleason sum
6
|
0 Participants
n=10 Participants
|
1 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
1 Participants
n=32 Participants
|
|
Biopsy Gleason sum
7
|
9 Participants
n=10 Participants
|
17 Participants
n=20 Participants
|
1 Participants
n=2 Participants
|
27 Participants
n=32 Participants
|
|
Biopsy Gleason sum
8-10
|
1 Participants
n=10 Participants
|
2 Participants
n=20 Participants
|
1 Participants
n=2 Participants
|
4 Participants
n=32 Participants
|
|
Radical prostatectomy (RP) Gleason sum
6
|
3 Participants
n=10 Participants
|
3 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
6 Participants
n=32 Participants
|
|
Radical prostatectomy (RP) Gleason sum
7
|
6 Participants
n=10 Participants
|
15 Participants
n=20 Participants
|
2 Participants
n=2 Participants
|
23 Participants
n=32 Participants
|
|
Radical prostatectomy (RP) Gleason sum
8-10
|
1 Participants
n=10 Participants
|
2 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
3 Participants
n=32 Participants
|
|
Preoperative clinical stage
T1c
|
6 Participants
n=10 Participants
|
13 Participants
n=20 Participants
|
2 Participants
n=2 Participants
|
21 Participants
n=32 Participants
|
|
Preoperative clinical stage
T2a
|
0 Participants
n=10 Participants
|
4 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
4 Participants
n=32 Participants
|
|
Preoperative clinical stage
T2b
|
3 Participants
n=10 Participants
|
2 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
5 Participants
n=32 Participants
|
|
Preoperative clinical stage
T2c
|
1 Participants
n=10 Participants
|
1 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
2 Participants
n=32 Participants
|
|
Pathologic stage
T2
|
6 Participants
n=10 Participants
|
10 Participants
n=20 Participants
|
2 Participants
n=2 Participants
|
18 Participants
n=32 Participants
|
|
Pathologic stage
T3a
|
3 Participants
n=10 Participants
|
7 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
10 Participants
n=32 Participants
|
|
Pathologic stage
T3b
|
0 Participants
n=10 Participants
|
3 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
3 Participants
n=32 Participants
|
|
Pathologic stage
TX N1
|
1 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=2 Participants
|
1 Participants
n=32 Participants
|
|
Any PSA Decline
|
1 Participants
n=5 Participants • Data for PSA decline was not collected for 5 participants from the Control Arm and 3 participants from the Low-dose arm.
|
4 Participants
n=17 Participants • Data for PSA decline was not collected for 5 participants from the Control Arm and 3 participants from the Low-dose arm.
|
1 Participants
n=2 Participants • Data for PSA decline was not collected for 5 participants from the Control Arm and 3 participants from the Low-dose arm.
|
6 Participants
n=24 Participants • Data for PSA decline was not collected for 5 participants from the Control Arm and 3 participants from the Low-dose arm.
|
|
Preoperative D'Amico risk
Low
|
0 Participants
n=10 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
1 Participants
n=20 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
0 Participants
n=2 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
1 Participants
n=32 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
|
Preoperative D'Amico risk
Intermediate
|
8 Participants
n=10 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
17 Participants
n=20 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
1 Participants
n=2 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
26 Participants
n=32 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
|
Preoperative D'Amico risk
High
|
2 Participants
n=10 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
2 Participants
n=20 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
1 Participants
n=2 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
5 Participants
n=32 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
|
Preoperative D'Amico risk
Undetectable day 90 PSA
|
4 Participants
n=5 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
17 Participants
n=20 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
2 Participants
n=2 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
23 Participants
n=27 Participants • Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm.
|
PRIMARY outcome
Timeframe: Day 15 post-interventionPopulation: Only 10 participants from the low-dose arm and 8 participants from the control arm had adequate paired tissue for evaluation, due to the lack of availability or inadequacy of either biopsy or radical prostatectomy. The 2 patients from the high-dose arm did not complete due to dose-limiting toxicity.
Outcome measures
| Measure |
Control Group
n=8 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Receive no intervention on Days 1-14. Surgery performed on Day 15.
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Low-dose Rapamycin (3mg)
n=10 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 3mg: Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
High-dose Rapamycin (6mg)
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 6mg: Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
|---|---|---|---|
|
Pharmocodynamically Optimal Dose (POD) of Rapamycin as Determined by Number of Participants With Greater Than or Equal to 60% Tumor S6 Kinase Inhibition by Immunohistochemistry (IHC).
|
1 Participants
|
5 Participants
|
—
|
PRIMARY outcome
Timeframe: Change from baseline to 15 days post-interventionPopulation: Only 10 participants from the low-dose arm and 8 participants from the control arm had adequate paired tissue for evaluation, due to the lack of availability or inadequacy of either biopsy or radical prostatectomy. The 2 patients from the high-dose arm did not complete due to dose-limiting toxicity.
Outcome measures
| Measure |
Control Group
n=8 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Receive no intervention on Days 1-14. Surgery performed on Day 15.
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Low-dose Rapamycin (3mg)
n=10 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 3mg: Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
High-dose Rapamycin (6mg)
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 6mg: Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
|---|---|---|---|
|
Median S6 Kinase Inhibition in Prostate Tumor Tissue at the POD
|
2 percentage of S6 kinase inhibition
Interval -6.0 to 30.0
|
58 percentage of S6 kinase inhibition
Interval -15.0 to 82.0
|
—
|
PRIMARY outcome
Timeframe: Change from baseline to 15 days post-interventionPopulation: Only 9 participants from the control group and 13 participants in the low-dose arm had evaluable tissue for analysis. Participants in the high dose arm did not complete the study due to serious adverse events.
Pharmocodynamic response was taken as ≥60% decrease in the H-score for S6 phosphorylation in the radical prostatectomy tumor tissue compared with the pretreatment (baseline) biopsy tumor tissue. The H-score is a semiquantitative measure of the percentage of cells scoring positive (0-100) multiplied by the intensity of staining (0-3).
Outcome measures
| Measure |
Control Group
n=9 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Receive no intervention on Days 1-14. Surgery performed on Day 15.
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Low-dose Rapamycin (3mg)
n=13 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 3mg: Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
High-dose Rapamycin (6mg)
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 6mg: Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
|---|---|---|---|
|
Pharmacodynamic Response as Assessed by Median Post-treatment S6 Activity H-score
|
140 score on a scale
Original data to report a dispersion measure cannot be located.
|
70 score on a scale
Original data to report a dispersion measure cannot be located.
|
—
|
SECONDARY outcome
Timeframe: Change from baseline to 15 days post-interventionPopulation: Data was not collected for this outcome measure
Snap-frozen prostate tissue was evaluated for tissue rapamycin levels.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Change from baseline to 15 days post-interventionPopulation: 0/2 participants tolerated this dose. Therefore, data for this outcome measure was not collected.
Snap-frozen prostate tissue was evaluated for tissue rapamycin levels.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Change from baseline to 15 days post-interventionPopulation: Only 7 participants from the control group and 10 participants in the low-dose arm had adequate paired tissue for analysis. Participants in the high dose arm did not complete the study due to serious adverse events.
Number of participants with change (increased, decreased or no change) in Akt phosphorylation as measured by immunohistochemistry (IHC)
Outcome measures
| Measure |
Control Group
n=7 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Receive no intervention on Days 1-14. Surgery performed on Day 15.
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Low-dose Rapamycin (3mg)
n=10 Participants
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 3mg: Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
High-dose Rapamycin (6mg)
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 6mg: Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
|---|---|---|---|
|
Number of Participants With Change in Akt Phosphorylation as Measured by Immunohistochemistry (IHC)
increased AKT phosphorylation
|
3 Participants
|
4 Participants
|
—
|
|
Number of Participants With Change in Akt Phosphorylation as Measured by Immunohistochemistry (IHC)
decreased AKT phosphorylation
|
3 Participants
|
4 Participants
|
—
|
|
Number of Participants With Change in Akt Phosphorylation as Measured by Immunohistochemistry (IHC)
no change in AKT phosphorylation
|
1 Participants
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: Change from baseline to 15 days post-interventionPopulation: Data was not collected for this outcome measure
Determine the relationship of PD target inhibition of S6 kinase activity with pretreatment PTEN loss by IHC in prostate cancer.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Change from baseline to 15 days post-interventionPopulation: Data was not collected for this outcome measure
p27 by IHC in prostate cancer.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Change from baseline to 15 days post-interventionPopulation: Data was not collected for this outcome measure
pretreatment biopsy compared to post-treatment radical prostatectomy specimen
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 14 days post-intervention, 90-days post-operativePopulation: Data was not collected for this outcome measure
Correlate PD efficacy as measured by downstream S6 kinase activity inhibition with markers of increased apoptosis (activated caspase 3) in prostate tumor specimens.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 14 days post-intervention, 90-days post-operativePopulation: Data was not collected for this outcome measure
Correlate PD efficacy as measured by downstream S6 kinase activity inhibition with markers of reduction in markers of proliferation (change in Ki-67) in prostate tumor specimens.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 14 days post-intervention, 90-days post-operativePopulation: Data was not collected for this outcome measure
Dose-limiting toxicity was defined as grade 3/4 neutropenia with fever lasting \>7 days, platelets of \<100,000/mm3 or associated with bleeding, grade ≥3 non-hematologic toxicity, or irreversible grade 2 toxicity related to rapamycine.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Change from baseline to Day 14Population: Data was not collected for this outcome measure
PSA response to daily rapamycin
Outcome measures
Outcome data not reported
Adverse Events
Control Group
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Low-dose Rapamycin (3mg)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
High-dose Rapamycin (6mg)
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Control Group
n=10 participants at risk
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Receive no intervention on Days 1-14. Surgery performed on Day 15.
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Low-dose Rapamycin (3mg)
n=20 participants at risk
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 3mg: Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
High-dose Rapamycin (6mg)
n=2 participants at risk
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 6mg: Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Severe thrombocytopenia
|
0.00%
0/10 • Day 90 post-operative
|
0.00%
0/20 • Day 90 post-operative
|
100.0%
2/2 • Day 90 post-operative
|
Other adverse events
| Measure |
Control Group
n=10 participants at risk
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Receive no intervention on Days 1-14. Surgery performed on Day 15.
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
Low-dose Rapamycin (3mg)
n=20 participants at risk
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 3mg: Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
High-dose Rapamycin (6mg)
n=2 participants at risk
Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy.
Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer.
Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Rapamycin 6mg: Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).
Radical prostatectomy: Radical prostatectomy performed on Day 15
|
|---|---|---|---|
|
Surgical and medical procedures
Post-operative ileus
|
10.0%
1/10 • Day 90 post-operative
|
10.0%
2/20 • Day 90 post-operative
|
0.00%
0/2 • Day 90 post-operative
|
|
Skin and subcutaneous tissue disorders
Maculopapular rash
|
0.00%
0/10 • Day 90 post-operative
|
5.0%
1/20 • Day 90 post-operative
|
0.00%
0/2 • Day 90 post-operative
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/10 • Day 90 post-operative
|
10.0%
2/20 • Day 90 post-operative
|
0.00%
0/2 • Day 90 post-operative
|
|
Infections and infestations
Stomatitis
|
0.00%
0/10 • Day 90 post-operative
|
10.0%
2/20 • Day 90 post-operative
|
100.0%
2/2 • Day 90 post-operative
|
|
Immune system disorders
Fever
|
0.00%
0/10 • Day 90 post-operative
|
0.00%
0/20 • Day 90 post-operative
|
100.0%
2/2 • Day 90 post-operative
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/10 • Day 90 post-operative
|
0.00%
0/20 • Day 90 post-operative
|
100.0%
2/2 • Day 90 post-operative
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/10 • Day 90 post-operative
|
5.0%
1/20 • Day 90 post-operative
|
0.00%
0/2 • Day 90 post-operative
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place