Ignite Creation Date:
2024-05-05 @ 4:39 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00280176
Status:
COMPLETED
Last Update Posted:
2012-02-14
First Post:
2006-01-18
Brief Title:
Bortezomib Fluorouracil and External-Beam Radiation Therapy in Treating Patients With Stage II Stage III or Stage IV Rectal Cancer
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
UNC Lineberger Comprehensive Cancer Center
Study Overview
Official Title:
Phase I Study of PS-341 in Combination With 5-Fluorouracil and External Beam Radiotherapy For The Treatment Of Locally Advanced And Metastatic Rectal Cancer
Status:
COMPLETED
Status Verified Date:
2012-02
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:
RATIONALE Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor Drugs used in chemotherapy such as fluorouracil work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Radiation therapy uses high-energy x-rays to kill tumor cells Giving bortezomib and fluorouracil together with radiation therapy may kill more tumor cells
PURPOSE This phase I trial is studying the side effects and best dose of bortezomib when given together with fluorouracil and external-beam radiation therapy in treating patients with stage II stage III or stage IV rectal cancer
PURPOSE This phase I trial is studying the side effects and best dose of bortezomib when given together with fluorouracil and external-beam radiation therapy in treating patients with stage II stage III or stage IV rectal cancer
Detailed Description:
OBJECTIVES
Primary
Determine the maximum tolerated dose of bortezomib when administered in combination with fluorouracil and external beam radiotherapy as preoperative or palliative treatment in patients with stage II-IV rectal adenocarcinoma
Determine the dose-limiting toxicities of this regimen in these patients
Secondary
Determine the dose-effect relationship of bortezomib on NF-kappa B activation induced by chemoradiotherapy
Determine downstream events induced by NF-kappa B activation
Determine downstream events related to activation of p53 in response to treatment with chemoradiotherapy and bortezomib
Determine the rate of complete pathologic remission in patients who undergo surgical resection of their primary tumor
Determine the gene expression pattern of tumors by cDNA microarray analysis before and during treatment with this regimen
OUTLINE This is a multicenter dose-escalation study of bortezomib
Patients receive bortezomib IV on days 1 4 8 11 22 25 29 and 32 and fluorouracil IV continuously on days 2-38 Patients also undergo external beam radiotherapy 5 days a week for 5½ weeks Treatment continues in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity
Patients undergo tissue biopsy at baseline and on days 1 and 2 Samples are collected and evaluated by tissue microarray analysis for NF-kappa B pathway activation cDNA analysis RNase protection assay and immunohistochemistry for analysis of downstream events induced by NF-kappa B activation and modified TdT-mediated dUTP nick-end label for analysis of apoptosis by DNA fragmentation NF-kappa B subunits are quantified by enzyme-linked immunosorbent assay Serum samples are collected at baseline and stored for future studies
After completion of study treatment patients are followed every 3 months for up to 2 years
Primary
Determine the maximum tolerated dose of bortezomib when administered in combination with fluorouracil and external beam radiotherapy as preoperative or palliative treatment in patients with stage II-IV rectal adenocarcinoma
Determine the dose-limiting toxicities of this regimen in these patients
Secondary
Determine the dose-effect relationship of bortezomib on NF-kappa B activation induced by chemoradiotherapy
Determine downstream events induced by NF-kappa B activation
Determine downstream events related to activation of p53 in response to treatment with chemoradiotherapy and bortezomib
Determine the rate of complete pathologic remission in patients who undergo surgical resection of their primary tumor
Determine the gene expression pattern of tumors by cDNA microarray analysis before and during treatment with this regimen
OUTLINE This is a multicenter dose-escalation study of bortezomib
Patients receive bortezomib IV on days 1 4 8 11 22 25 29 and 32 and fluorouracil IV continuously on days 2-38 Patients also undergo external beam radiotherapy 5 days a week for 5½ weeks Treatment continues in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity
Patients undergo tissue biopsy at baseline and on days 1 and 2 Samples are collected and evaluated by tissue microarray analysis for NF-kappa B pathway activation cDNA analysis RNase protection assay and immunohistochemistry for analysis of downstream events induced by NF-kappa B activation and modified TdT-mediated dUTP nick-end label for analysis of apoptosis by DNA fragmentation NF-kappa B subunits are quantified by enzyme-linked immunosorbent assay Serum samples are collected at baseline and stored for future studies
After completion of study treatment patients are followed every 3 months for up to 2 years
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 |
|---|---|---|---|
| CDR0000549844 | OTHER | PDQ number | None |