- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00425503
PS-341 Followed by Removal of Prostate for Those With Prostate Cancer
H-11047: A Study of PS-341 Followed by Radical Prostatectomy for Patients With Adenocarcinoma of the Prostate (Spore #: 11-01-30-13)
Study Overview
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 0.067 mg/kg/dose or 0.80 mg/m2/dose. The PS-341 dose selected for this study, 1.6 mg/m2, 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 M.D. 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 1.8 mg/m2.11,12 The LTs were observed at 2.0 mg/m2 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 1.60 mg/m2, 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 1.65 mg/m2 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-Hodgkin's 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 phase.14 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Scott Department of Urology, Baylor College of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologic proof of prostatic adenocarcinoma without evidence of regional and/or distant metastasis, clinical stage T1, T2 or T3 with high grade disease (Gleason's grade 7 or above).
- Recent (less than or equal to 6 weeks prior to study entry) negative bone scan and CT scan of abdomen/pelvis.
- Appropriate surgical candidate for radical prostatectomy and a performance status of less than or equal to 2 (Zubrod scale).
- Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count greater than or equal to 1,500 and platelet count of greater than or equal to 100,000, adequate hepatic function with a bilirubin less than or equal to 1.5 mg % and SGPT less than 2.5x the upper limits of normal, adequate renal function defined as serum creatinine less than or equal to 2.0 mg %.
- Patients must have normal coagulation profile (PT, PTT) and no history of substantial non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to local use only (for control of central line patency).
- Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with the policies of the institution.
- Patients screened and found eligible for the study, but not wanting to participate for any reason, will be followed along with the patients enrolled in the study in an effort to obtain outcome information (as historical information for design of future trials).
- No evidence of bifascicular block or active ischemia on EKG.
- Patients must have no history of congestive heart failure or previous MI.
Exclusion Criteria:
- Previous or current hormonal treatment, chemotherapy, radiation therapy, immunotherapy or other investigational status drug.
- Unable to tolerate transrectal ultrasound.
- Patients who are not appropriate surgical candidates for radical prostatectomy based on the evaluation of co-existent medical diseases and competing causes of death. Patients with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorder are not eligible.
- Patients who are HIV positive or have chronic hepatitis B or C infections are not eligible.
- Patients on steroid medications are not eligible.
- Patients with uncontrolled and symptomatic orthostatic hypotension or uncontrolled hypertension are not eligible.
- Patients with significant arteriosclerotic disease, as defined by a previous arterial bypass, claudication limiting activity, or a history of cerebrovascular events within the last year (including TIA) are not eligible.
- Patients with diabetes mellitus requiring insulin or oral hypoglycemics for more than 5 years are not eligible.
- Patient has greater than or equal to grade 1 peripheral neuropathy within 14 days before enrollment.
- Hypersensitivity to boron, mannitol, or bortezomib.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Purpose of the Present Study is to Assess the Safety of PS-341 as a Pretreatment in Patients Who Are to Undergo a Radical Prostatectomy. Poor Wound Healing and Excessive Bleeding, With Historical Rates of <1% and 10% Respectively Will be Measured.
Time Frame: Poor wound healing (dehiscence of fascia during the first postoperative week) and bleeding 24 hours after surgery
|
Pour wound healing is defined in the protocol as dehiscence of fascia during the first postoperative week.
Excessive bleeding is defined in the protocol as greater than 2 units of blood required during the first 24 hours after surgery.
|
Poor wound healing (dehiscence of fascia during the first postoperative week) and bleeding 24 hours after surgery
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Teresa Hayes, M.D., Ph.D., Baylor College of Medicine
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-11047
- P50CA058204 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Prostate Neoplasms
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Regeneron Pharmaceuticals; Prostate Cancer FoundationWithdrawnStage III Prostate Cancer | Stage IV Prostate Cancer | Stage IVA Prostate Cancer | Stage IVB Prostate Cancer | Stage IIIA Prostate Cancer | Stage IIIB Prostate Cancer | Stage IIIC Prostate Cancer
-
Mayo ClinicNational Cancer Institute (NCI)TerminatedProstate Adenocarcinoma | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
DendreonCompletedProstate Cancer | Prostate Neoplasms | Cancer of the Prostate | Neoplasms, Prostate | Prostatic Cancer | Neoplasms, Prostatic | Cancer of ProstateAustria, France, Netherlands, United Kingdom
-
University of California, IrvineCompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Ohio State University Comprehensive Cancer CenterRiverside Methodist HospitalCompletedStage I Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Roswell Park Cancer InstituteUniversity of PittsburghCompletedProstate Cancer | Prostate Neoplasms | Cancer of the Prostate | Neoplasms, Prostate | Prostatic Cancer | Neoplasms, Prostatic | Cancer of ProstateUnited States
-
Sidney Kimmel Comprehensive Cancer Center at Johns...National Cancer Institute (NCI)TerminatedMetastatic Prostate Carcinoma | Prostate Adenocarcinoma | Stage IV Prostate Cancer | Hormone-Resistant Prostate CancerUnited States
-
Barbara Ann Karmanos Cancer InstituteGenentech, Inc.CompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedProstate Adenocarcinoma | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
Clinical Trials on PS-341 (bortezomib)
-
Mayo ClinicNational Cancer Institute (NCI)CompletedLeukemia | Chronic Myeloproliferative DisordersUnited States
-
M.D. Anderson Cancer CenterMillennium Pharmaceuticals, Inc.CompletedLymphoma, B-CellUnited States
-
M.D. Anderson Cancer CenterMillennium Pharmaceuticals, Inc.CompletedLeukemiaUnited States
-
M.D. Anderson Cancer CenterMillennium Pharmaceuticals, Inc.CompletedOvarian Cancer | Fallopian Tube Cancer | Primary Peritoneal CancerUnited States
-
M.D. Anderson Cancer CenterCompletedMultiple MyelomaUnited States
-
Rasim GucalpMillennium Pharmaceuticals, Inc.TerminatedNon-small Cell Lung CancerUnited States
-
Beijing Chao Yang HospitalEnrolling by invitationMultiple Myeloma | BortezomibChina
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedGraft-versus-Host DiseaseUnited States
-
Mayo ClinicCompletedRefractory Multiple MyelomaUnited States
-
Jules Bordet InstituteCompletedCarcinoma Breast Stage IVBelgium