Ignite Creation Date:
2024-05-05 @ 5:18 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00425503
Status:
COMPLETED
Last Update Posted:
2014-04-21
First Post:
2007-01-22
Brief Title:
PS-341 Followed by Removal of Prostate for Those With Prostate Cancer
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
H-11047 A Study of PS-341 Followed by Radical Prostatectomy for Patients With Adenocarcinoma of the Prostate Spore 11-01-30-13
Status:
COMPLETED
Status Verified Date:
2014-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Following pretreatment evaluation patients receive PS-341 by intravenous push weekly for 4 consecutive weeks followed by a 24-72 hour rest period This schedule consists of one treatment cycle Upon the completion of 4 weeks of PS-341 followed by a 24-72 hour rest period radical prostatectomy will be performed Surgery will be delayed if there is any bleeding abnormality bleeding time greater than 10 minutes and until platelet count is more than or equal to 100000 and coagulation profile PT PTT is normal If at the time of surgery a patient is found to have positive lymph nodes prostatectomy will be abandoned the prostate will be biopsied and the patient will be offered other treatment modalities hormones radiation therapy
Detailed Description:
In murine and human xenograft tumor models administration of PS-341 weekly was associated with significant antitumor activity In primate studies using a schedule of twice weekly for six weeks the highest PS-341 dose not associated with severe irreversible toxicity was 0067 mgkgdose or 080 mgm2dose The PS-341 dose selected for this study 16 mgm2 and the dose regimen of a 4-week treatment schedule PS-341 once weekly for four weeks on days 1 8 15 and 22 is supported by preclinical data and data collected in the completed Phase I studies conducted in advanced solid tumors and hematologic malignancies In the Phase I dose escalation study conducted at the MD Anderson Cancer Center that is sponsored by Millennium Pharmaceuticals in patients with solid tumors in which PS-341 was administered once per week for four weeks followed by a 14-day rest period 35-day cycle the observed MTD was 18 mgm21112 The LTs were observed at 20 mgm2 and included hypotension diarrhea and fatigue Fifty-three patients were treated in this study and received a maximum of 15 cycles At the dose level 160 mgm2 70-75 20S proteasome inhibition and peripheral blood was achieved at this dose One false response a major radiographic response of retroperitoneal lymph nodes without PSA change was noted in a prostate cancer patient and a second prostate patient had radiographic stabilization of a retroperitoneal lymph node with an unchanged PSA One partial response a major radiographic response of retroperitoneal lymph nodes without PSA change was noted in a prostate cancer patient and a second prostate patient had radiographic stabilization of a retroperitoneal lymph node with an unchanged PSA One partial response a major radiographic response of retroperitoneal lymph nodes without PSA change was noted in a prostate cancer patient and a second prostate patient had radiographic stabilization of a retroperitoneal lymph node with an unchanged PSA Further company-sponsored trial at Memorial Sloan-Kettering Cancer Center is assessing twice weekly administration for two weeks every three weeks This trial is currently dosing at 165 mgm2 and a proteasome inhibition is in the range of 74-78 One prostate cancer patient has had a significant decrease in PSA levels There have been no dose-limiting toxicities noted in either of the studies to date although drug associated toxicities have included fatigue fever nausea and vomiting anorexia diarrhea and thrombocytopenia The NCI is sponsoring three Phase I trials of PS-341 administered IV twice weekly days 1 and 4 One trial is assessing an every other week administration of PS-341 in patients with solid tumors and non-Hodgkins lymphoma A weekly times 4 every six weeks schedule is being evaluated in patients with solid tumors and B cell lymphoproliferative disorders A third trial is evaluating the same administration schedule in patients with acute myeloid leukemias myelodysplastic syndromes and chronic myeloid leukemia in blast phase14 These trials have all recently opened Based on these observations PS-341 will be administered once a week for 4 weeks with a 24-72 hour recovery period prior to radical prostatectomy
We propose to study the in vivo effect of systemic treatment with PS-341 doing correlative scientific markers assessing apoptosis evaluation of protease protein targets angiogenesis markers We do not anticipate any perioperative morbidity when prostatectomy is performed 24-72 hours following the last drug dose A residual drug activity may impact transiently on wound healing or on operative blood loss but this effect if present should dissipate within a short period while proteasome activity recovers in all normal tissues Long term effects on the vesico-urethral anastomosis or the recovery of bladder and erectile functions are not expected
At the same time obtaining the prostate within 72 hours at most following the last drug dose should enable us to evaluate multiple protein markers while still influenced by proteasome inhibition and to document biologic activity of the drug in the target organ
We propose to study the in vivo effect of systemic treatment with PS-341 doing correlative scientific markers assessing apoptosis evaluation of protease protein targets angiogenesis markers We do not anticipate any perioperative morbidity when prostatectomy is performed 24-72 hours following the last drug dose A residual drug activity may impact transiently on wound healing or on operative blood loss but this effect if present should dissipate within a short period while proteasome activity recovers in all normal tissues Long term effects on the vesico-urethral anastomosis or the recovery of bladder and erectile functions are not expected
At the same time obtaining the prostate within 72 hours at most following the last drug dose should enable us to evaluate multiple protein markers while still influenced by proteasome inhibition and to document biologic activity of the drug in the target organ
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P50CA058204 | NIH | None | httpsreporternihgovquickSearchP50CA058204 |