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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA006973 | U.S. NIH Grant/Contract | View source | |
| CDR0000468942 | Other Identifier | other | |
| NA_00001011 | Other Identifier | JHM IRB |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy, such as sirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This clinical trial is studying the best dose of sirolimus and to see how well it works before surgery in treating patients with advanced localized prostate cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive oral sirolimus (rapamycin) once daily on days 1-14 in the absence of unacceptable toxicity.
Cohorts of 12-21 patients receive escalating doses of rapamycin until the pharmacodynamically optimal dose is determined.
Patients undergo radical prostatectomy on day 15.
Patients undergo blood collection and tumor biopsies periodically during study for pharmacologic and correlative biomarker studies.
After completion of study treatment, patients are followed at 30 and 90 days.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | Active Comparator | 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. |
|
| Low-dose Rapamycin (3mg) | Experimental | 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). |
|
| High-dose Rapamycin (6mg) | Experimental | 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). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rapamycin 3mg | Drug | 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). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Day 15 post-intervention | |
| Median S6 Kinase Inhibition in Prostate Tumor Tissue at the POD | Change from baseline to 15 days post-intervention | |
| Pharmacodynamic Response as Assessed by Median Post-treatment S6 Activity H-score | 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). | Change from baseline to 15 days post-intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Response of Rapamycin 3mg as Assessed by Whole Blood Analysis | Snap-frozen prostate tissue was evaluated for tissue rapamycin levels. | Change from baseline to 15 days post-intervention |
| Pharmacokinetic Response of Rapamycin 6mg as Assessed by Whole Blood Analysis |
Not provided
DISEASE CHARACTERISTICS:
Histologically determined adenocarcinoma of the prostate
No metastatic prostate cancer, including bone, visceral, brain, and lymph node metastases
Tumor Gleason score sum of 7-10 (4+3 and 3+4 allowed) with tumor involving at least 2 discrete core biopsy sections
Scheduled to undergo radical prostatectomy
No other subtypes of prostate cancer, including any of the following:
PATIENT CHARACTERISTICS:
ECOG performance status 0-1
WBC > 3,500/mm^3
Absolute neutrophil count > 1,500/mm^3
Platelet count > 100,000/mm^3
Hemoglobin > 9 g/dL
Creatinine < 2.0 mg/dL
Bilirubin < 2 mg/dL
ALT and AST < 2 times upper limit of normal (ULN)
Alkaline phosphatase < 2 times ULN
Triglycerides and total cholesterol < 2 times ULN
No history of allergy to sirolimus (rapamycin) or its derivatives
No uncontrolled medical condition that would increase risk or limit compliance with study requirements, including the following:
No active infections
No other concurrent malignancy
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
No prior chemotherapy, biologic therapy, radiotherapy, or immunotherapy for prostate cancer
No concurrent chronic treatment with immunosuppressants or medications that interfere with the metabolism of sirolimus (rapamycin)
No concurrent medication or agents that would interfere with the metabolism or excretion of rapamycin or its derivatives, including any of the following:
At least 7 days since prior herbal medicines and medications, including any of the following:
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| Name | Affiliation | Role |
|---|---|---|
| Michael A. Carducci, MD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21231 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20501622 | Result | Armstrong AJ, Netto GJ, Rudek MA, Halabi S, Wood DP, Creel PA, Mundy K, Davis SL, Wang T, Albadine R, Schultz L, Partin AW, Jimeno A, Fedor H, Febbo PG, George DJ, Gurganus R, De Marzo AM, Carducci MA. A pharmacodynamic study of rapamycin in men with intermediate- to high-risk localized prostate cancer. Clin Cancer Res. 2010 Jun 1;16(11):3057-66. doi: 10.1158/1078-0432.CCR-10-0124. Epub 2010 May 25. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| FG002 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | 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. | Posted | Count of Participants | Participants | Day 15 post-intervention |
|
Day 90 post-operative
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Severe thrombocytopenia | Blood and lymphatic system disorders | NCI CTC v3.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Post-operative ileus | Surgical and medical procedures | NCI CTC v3.0 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Andrew Armstrong, MD ScM FACP | Duke University | (919) 668-8797 | andrew.armstrong@duke.edu |
Not provided
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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Not provided
Not provided
Not provided
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Not provided
|
| Rapamycin 6mg | Drug | 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 | Procedure | Radical prostatectomy performed on Day 15 |
|
Snap-frozen prostate tissue was evaluated for tissue rapamycin levels. |
| Change from baseline to 15 days post-intervention |
| Number of Participants With Change in Akt Phosphorylation as Measured by Immunohistochemistry (IHC) | Number of participants with change (increased, decreased or no change) in Akt phosphorylation as measured by immunohistochemistry (IHC) | Change from baseline to 15 days post-intervention |
| PTEN Loss as Measured by Immunohistochemistry (IHC) | Determine the relationship of PD target inhibition of S6 kinase activity with pretreatment PTEN loss by IHC in prostate cancer. | Change from baseline to 15 days post-intervention |
| p27 as Measured by Immunohistochemistry (IHC) | p27 by IHC in prostate cancer. | Change from baseline to 15 days post-intervention |
| Change in Gleason Sum | pretreatment biopsy compared to post-treatment radical prostatectomy specimen | Change from baseline to 15 days post-intervention |
| Increased Apoptosis as Measured by Activated Caspase 3 | Correlate PD efficacy as measured by downstream S6 kinase activity inhibition with markers of increased apoptosis (activated caspase 3) in prostate tumor specimens. | Baseline, 14 days post-intervention, 90-days post-operative |
| Reduction in Proliferation as Measured by Decrease in Ki-67 | 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. | Baseline, 14 days post-intervention, 90-days post-operative |
| Toxicity as Per National Cancer Institute Common Toxicity Criteria v3.0 | 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. | Baseline, 14 days post-intervention, 90-days post-operative |
| Activity of Rapamycin as Measured by Prostate Specific Antigen (PSA) Response Prior to Surgery | PSA response to daily rapamycin | Change from baseline to Day 14 |
| University of Michigan Comprehensive Cancer Center |
| Ann Arbor |
| Michigan |
| 48109-0942 |
| United States |
| Duke Comprehensive Cancer Center | Durham | North Carolina | 27710 | United States |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | All participants were male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index | Median | Standard Deviation | kg/m2 |
|
| Biopsy Gleason sum | The Gleason sum ranges from 2-10 with a higher score reflecting less-differentiated tumors with worse prognosis. The total is a sum of two numbers which are based on the microscopic appearance of cells. The first number is the score based on the dominant, cell morphology (scored 1-5) and the second number is based on the highest grade of the non-dominant cell pattern (scored 1-5). | Count of Participants | Participants |
|
| Radical prostatectomy (RP) Gleason sum | The Gleason sum ranges from 2-10 with a higher score reflecting less-differentiated tumors with worse prognosis. The total is a sum of two numbers which are based on the microscopic appearance of cells. The first number is the score based on the dominant, cell morphology (scored 1-5) and the second number is based on the highest grade of the non-dominant cell pattern (scored 1-5). | Count of Participants | Participants |
|
| Preoperative clinical stage | Clinical stage is estimated based on results of physical exam, biopsy or any imaging tests. Staging is defined by the American Joint Committee on Cancer (AJCC) TNM system where T= primary tumor, N= spread to nearby lymph nodes, M= metastasis, Grade Group 1 through 5 (based on Gleason score, higher grade group reflects higher Gleason score), and further letter ("a" through "c" staging. A lower number reflects less spread of cancer and a lower letter reflects a lower stage. | Count of Participants | Participants |
|
| Pathologic stage | Pathological stage is assessed by analyzing tissue collected from prostatectomy. Staging is defined by the American Joint Committee on Cancer (AJCC) TNM system where T= primary tumor, N= spread to nearby lymph nodes, M= metastasis, Grade Group 1 through 5 (based on Gleason score, higher grade group reflects higher Gleason score), and further letter ("a" through "c" staging. A lower number reflects less spread of cancer and a lower letter reflects a lower stage. | Count of Participants | Participants |
|
| Any PSA Decline | Data for PSA decline was not collected for 5 participants from the Control Arm and 3 participants from the Low-dose arm. | Count of Participants | Participants |
|
| Preoperative D'Amico risk | Data for Undetectable day 90 PSA was not collected for 5/10 participants from the Control Arm. | Count of Participants | Participants |
|
| OG001 | 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 |
| OG002 | 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 |
|
|
| Primary | Median S6 Kinase Inhibition in Prostate Tumor Tissue at the POD | 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. | Posted | Median | Inter-Quartile Range | percentage of S6 kinase inhibition | Change from baseline to 15 days post-intervention |
|
|
|
| Primary | Pharmacodynamic Response as Assessed by Median Post-treatment S6 Activity H-score | 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). | 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. | Posted | Median | Full Range | score on a scale | Change from baseline to 15 days post-intervention |
|
|
|
| Secondary | Pharmacokinetic Response of Rapamycin 3mg as Assessed by Whole Blood Analysis | Snap-frozen prostate tissue was evaluated for tissue rapamycin levels. | Data was not collected for this outcome measure | Posted | Change from baseline to 15 days post-intervention |
|
|
| Secondary | Pharmacokinetic Response of Rapamycin 6mg as Assessed by Whole Blood Analysis | Snap-frozen prostate tissue was evaluated for tissue rapamycin levels. | 0/2 participants tolerated this dose. Therefore, data for this outcome measure was not collected. | Posted | Change from baseline to 15 days post-intervention |
|
|
| Secondary | Number of Participants With Change in Akt Phosphorylation as Measured by Immunohistochemistry (IHC) | Number of participants with change (increased, decreased or no change) in Akt phosphorylation as measured by immunohistochemistry (IHC) | 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. | Posted | Count of Participants | Participants | Change from baseline to 15 days post-intervention |
|
|
|
| Secondary | PTEN Loss as Measured by Immunohistochemistry (IHC) | Determine the relationship of PD target inhibition of S6 kinase activity with pretreatment PTEN loss by IHC in prostate cancer. | Data was not collected for this outcome measure | Posted | Change from baseline to 15 days post-intervention |
|
|
| Secondary | p27 as Measured by Immunohistochemistry (IHC) | p27 by IHC in prostate cancer. | Data was not collected for this outcome measure | Posted | Change from baseline to 15 days post-intervention |
|
|
| Secondary | Change in Gleason Sum | pretreatment biopsy compared to post-treatment radical prostatectomy specimen | Data was not collected for this outcome measure | Posted | Change from baseline to 15 days post-intervention |
|
|
| Secondary | Increased Apoptosis as Measured by Activated Caspase 3 | Correlate PD efficacy as measured by downstream S6 kinase activity inhibition with markers of increased apoptosis (activated caspase 3) in prostate tumor specimens. | Data was not collected for this outcome measure | Posted | Baseline, 14 days post-intervention, 90-days post-operative |
|
|
| Secondary | Reduction in Proliferation as Measured by Decrease in Ki-67 | 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. | Data was not collected for this outcome measure | Posted | Baseline, 14 days post-intervention, 90-days post-operative |
|
|
| Secondary | Toxicity as Per National Cancer Institute Common Toxicity Criteria v3.0 | 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. | Data was not collected for this outcome measure | Posted | Baseline, 14 days post-intervention, 90-days post-operative |
|
|
| Secondary | Activity of Rapamycin as Measured by Prostate Specific Antigen (PSA) Response Prior to Surgery | PSA response to daily rapamycin | Data was not collected for this outcome measure | Posted | Change from baseline to Day 14 |
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 1 |
| 10 |
| EG001 | 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 | 0 | 20 | 0 | 20 | 8 | 20 |
| EG002 | 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 | 0 | 2 | 2 | 2 | 2 | 2 |
| Maculopapular rash | Skin and subcutaneous tissue disorders | NCI CTC v3.0 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | NCI CTC v3.0 | Non-systematic Assessment | Grade 1-2 Neutropenia without fever |
|
| Stomatitis | Infections and infestations | NCI CTC v3.0 | Non-systematic Assessment |
|
| Fever | Immune system disorders | NCI CTC v3.0 | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | NCI CTC v3.0 | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | NCI CTC v3.0 | Non-systematic Assessment | Grade 1 thrombocytopenia |
|
Not provided
Not provided
Not provided
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| Male |
|
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| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| no change in AKT phosphorylation |
|