Ignite Creation Date:
2024-05-05 @ 11:37 PM
Last Modification Date:
2024-10-26 @ 10:36 AM
Study NCT ID:
NCT01374789
Status:
TERMINATED
Last Update Posted:
2015-06-03
First Post:
2011-03-30
Brief Title:
PURO Panitumumab in Combination With GemcitabineCisplatin in Advanced Urothelial Cancer
Sponsor:
WiSP Wissenschaftlicher Service Pharma GmbH
Organization:
WiSP Wissenschaftlicher Service Pharma GmbH
Study Overview
Official Title:
PURO - An Open-label Randomised Multicentre Phase II Study to Evaluate the Efficacy of Chemotherapy With Gemcitabine and Cisplatin in Combination With the EGF Receptor Antibody Panitumumab GemCisP Versus GemCis in the First-line Therapy of Locally AdvancedMetastatic Urothelial Carcinoma in Patients With Wild-type HRAS
Status:
TERMINATED
Status Verified Date:
2015-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The study was terminated due to insufficient recruitment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PURO
Brief Summary:
The primary objective of the study is to assess the efficacy of the combination consisting of gemcitabinecisplatin and panitumumab in patients with urothelial carcinoma and wild-type HRAS non-mutated status The progression-free survival rate at 12 months will be compared to expectations derived from historical data which are verified by a randomised control group without the antibody
Detailed Description:
Mutation of ras oncogenes is frequently observed in human tumours and occurs in approximately 30 of all cancer types Frequent mutation hot spots occur in codon 12 glycine to valine codon 13 glycine to cysteine and codon 61 glutamine to arginine lysine and leucine Bonner et al 1993 Levesque et al 1993 Point mutations in ras genes result in blockade of intrinsic GTPase activity the physiological mechanism that switches off ras GTPases The consequence is persistent up-regulation of the signal pathway and increased cell proliferation The first HRAS mutation in association with bladder cancer was described during establishment of the human urinary bladder carcinoma cell line T24 In further studies a research group led by Fitzgerald was able to demonstrate that HRAS gene mutations were present in the urine sediment of up to 44 of patients with urinary bladder cancer Fitzgerald et al 1995
Viola et al subsequently investigated whether an increased mutation rate is accompanied by increased expression of ras proteins in bladder cancer It was shown that there is indeed increased expression of ras proteins in dedifferentiated tumours and carcinomas in situ whereas highly differentiated tumours do not exhibit this rate of expression Viola et al 1985
At present there is no clinical evidence that the findings of an obvious lack of activity of EGFR antibodies in colorectal cancer with RAS-related mutations is likewise valid in urothelial carcinoma However as it is the aim of this study to detect a first signal of activity in this type of cancer and the chance of missing such evidence in a phase II trial with limited patient numbers is high anyway it seems sensible not to miss this opportunity of enrichment In case of a clearly positive signal of efficacy in the present trial a subsequent phase II study may focus on HRAS mutated tumors
Overexpression of the EGF receptor in bladder cancer has been described by many research groups Colquhuon Mellon 2002 and is associated with an advanced stage of the tumour progression of the tumour and a poor clinical prognosis The EGFR antibody cetuximab Erbitux has been investigated in a human urothelial carcinoma cell line and in a mouse model with human bladder carcinoma Cetuximab was found to inhibit tumorigenesis and metastatic progression in vivo and in vitro by means of suppression of angiogenesis and simultaneous induction of apoptosis Perotte et al 1999 Inoue et al 2000 Similar results have also been reported in urothelial carcinoma for the tyrosine kinase inhibitor gefitinib Villares et al 2007 Shrader et al 2007
There are currently two on-going studies of cetuximab in metastatic bladder cancer a randomised phase II study of first-line treatment with Gemcitabine and Cisplatin - Erbitux NCT00645593 and a randomised phase II study of second-line treatment with Erbitux - Paclitaxel NCT00350025
The HRAS mutation rate in urothelial carcinoma is approximately 40 The primary objective of the study is to assess the efficacy of the combination consisting of gemcitabinecisplatin and panitumumab in patients with wild-type HRAS non-mutated status The progression-free survival rate at 12 months will be compared to expectations derived from historical data which are verified by a randomised control group without the antibody
Viola et al subsequently investigated whether an increased mutation rate is accompanied by increased expression of ras proteins in bladder cancer It was shown that there is indeed increased expression of ras proteins in dedifferentiated tumours and carcinomas in situ whereas highly differentiated tumours do not exhibit this rate of expression Viola et al 1985
At present there is no clinical evidence that the findings of an obvious lack of activity of EGFR antibodies in colorectal cancer with RAS-related mutations is likewise valid in urothelial carcinoma However as it is the aim of this study to detect a first signal of activity in this type of cancer and the chance of missing such evidence in a phase II trial with limited patient numbers is high anyway it seems sensible not to miss this opportunity of enrichment In case of a clearly positive signal of efficacy in the present trial a subsequent phase II study may focus on HRAS mutated tumors
Overexpression of the EGF receptor in bladder cancer has been described by many research groups Colquhuon Mellon 2002 and is associated with an advanced stage of the tumour progression of the tumour and a poor clinical prognosis The EGFR antibody cetuximab Erbitux has been investigated in a human urothelial carcinoma cell line and in a mouse model with human bladder carcinoma Cetuximab was found to inhibit tumorigenesis and metastatic progression in vivo and in vitro by means of suppression of angiogenesis and simultaneous induction of apoptosis Perotte et al 1999 Inoue et al 2000 Similar results have also been reported in urothelial carcinoma for the tyrosine kinase inhibitor gefitinib Villares et al 2007 Shrader et al 2007
There are currently two on-going studies of cetuximab in metastatic bladder cancer a randomised phase II study of first-line treatment with Gemcitabine and Cisplatin - Erbitux NCT00645593 and a randomised phase II study of second-line treatment with Erbitux - Paclitaxel NCT00350025
The HRAS mutation rate in urothelial carcinoma is approximately 40 The primary objective of the study is to assess the efficacy of the combination consisting of gemcitabinecisplatin and panitumumab in patients with wild-type HRAS non-mutated status The progression-free survival rate at 12 months will be compared to expectations derived from historical data which are verified by a randomised control group without the antibody
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 |
|---|---|---|---|
| 2009-015119-42 | EUDRACT_NUMBER | None | None |
| GMIHO-0072008 | OTHER | GMIHO mbh | None |