Ignite Creation Date:
2024-05-05 @ 11:17 PM
Last Modification Date:
2024-10-26 @ 10:31 AM
Study NCT ID:
NCT01293851
Status:
TERMINATED
Last Update Posted:
2019-12-05
First Post:
2011-01-25
Brief Title:
Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Nerve Damage
Sponsor:
National Institute of Nursing Research NINR
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Characterization of the Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Peripheral Neuropathy Progression
Status:
TERMINATED
Status Verified Date:
2012-11-13
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:
Background
- Docetaxel the most commonly used drug for the treatment of invasive breast cancer has been shown to prolong the lives of women with breast cancer and prevent the cancer from spreading or returning However docetaxel is known to cause nerve damage including numbness tingling and pain in 50 to 90 percent of breast cancer patients This nerve damage is called peripheral neuropathy and can be so severe that treatment with docetaxel may need to be stopped Researchers are interested in studying docetaxel-related nerve damage to determine whether certain genetic factors may predispose women to developing this condition and to more closely investigate the specific effects of docetaxel on the nervous system
Objectives
- To examine nerve damage in women with breast cancer who are being treated with docetaxel
Eligibility
- Women at least 18 years of age who have been diagnosed with invasive breast cancer and are scheduled to have docetaxel treatment
Design
Participants will be screened with a full medical history and physical examination as well as blood and urine tests and imaging studies
This study requires seven visits one before the start of chemotherapy and six after the scheduled treatment visits Study procedures at each visit will take 30 to 45 minutes and will be done in parallel with scheduled chemotherapy visits
At the first visit participants will provide blood samples complete questionnaires to rate and describe any existing pain numbness or tingling in hands and feet before the start of chemotherapy have nerve conduction tests and have a skin biopsy
At each visit following docetaxel treatment participants will complete questionnaires to rate and describe any pain numbness or tingling during the course of chemotherapy Participants will provide blood samples at every visit and have nerve conduction tests during the second fourth and sixth visits Participants will also have a second skin biopsy either from a site that appears to be experiencing nerve damage or for those who are not developing nerve damage symptoms from a site near the first biopsy location
- Docetaxel the most commonly used drug for the treatment of invasive breast cancer has been shown to prolong the lives of women with breast cancer and prevent the cancer from spreading or returning However docetaxel is known to cause nerve damage including numbness tingling and pain in 50 to 90 percent of breast cancer patients This nerve damage is called peripheral neuropathy and can be so severe that treatment with docetaxel may need to be stopped Researchers are interested in studying docetaxel-related nerve damage to determine whether certain genetic factors may predispose women to developing this condition and to more closely investigate the specific effects of docetaxel on the nervous system
Objectives
- To examine nerve damage in women with breast cancer who are being treated with docetaxel
Eligibility
- Women at least 18 years of age who have been diagnosed with invasive breast cancer and are scheduled to have docetaxel treatment
Design
Participants will be screened with a full medical history and physical examination as well as blood and urine tests and imaging studies
This study requires seven visits one before the start of chemotherapy and six after the scheduled treatment visits Study procedures at each visit will take 30 to 45 minutes and will be done in parallel with scheduled chemotherapy visits
At the first visit participants will provide blood samples complete questionnaires to rate and describe any existing pain numbness or tingling in hands and feet before the start of chemotherapy have nerve conduction tests and have a skin biopsy
At each visit following docetaxel treatment participants will complete questionnaires to rate and describe any pain numbness or tingling during the course of chemotherapy Participants will provide blood samples at every visit and have nerve conduction tests during the second fourth and sixth visits Participants will also have a second skin biopsy either from a site that appears to be experiencing nerve damage or for those who are not developing nerve damage symptoms from a site near the first biopsy location
Detailed Description:
Objective Chemotherapy-induced peripheral neuropathy CIPN is one of the most debilitating side effects of neurotoxic chemotherapy and can significantly interfere with patient quality of life QOL and the administration of antineoplastic therapy There is no currently approved safe and effective treatment for CIPN This protocol will explore the molecular-genetic mechanisms associated with the natural history of CIPN progression by 1 identification of differentially expressed genes and proteins as biomarkers for the onset of CIPN 2 evaluation of the relationship between biomarkers and the severity of CIPN during the observation period and 3 determining the relationship between molecular-genetic biomarkers morphological changes in small nerve fiber and the severity of neuropathic symptoms
Study population Cancer patients who plan to receive chemotherapy treatment with either taxane class vinca alkaloid class platinum compounds or bortezomib
Design This is a prospective exploratory natural history study to identify the molecular-genetic mechanisms involved in chemotherapy-induced neuropathy in cancer patients A physician-based neuropathy scale patient neurotoxocity questionnaire and the total neuropathy score will be used to measure the severity of peripheral neuropathy at baseline and after completion of each cycle of chemotherapy infusion Whole peripheral blood and skin biopsy only from patients who consent to biopsies will be collected at baseline and after a subsequent infusion cycle to evaluate geneprotein expression and immunohistochemical labeling at peripheral sites of neuropathic injury Microarray gene expression analysis will be employed to identify differential regulation of genes involved in the development of CIPN at the different time points compared with gene expression from the baseline samples Genes of interest will be validated by qRT-PCR to identify novel pharmacological targets to be evaluated in future prospective studies Protein levels corresponding to the changes in gene expression will be evaluated using ELISA and verified by Western blotting
Outcome measures The primary outcome of the study will be the changes in gene and protein expression in the peripheral blood and skin biopsy among cancer patients undergoing chemotherapy The secondary outcome will be the relationship between the molecular-genetic biomarkers identified and the presence of peripheral neuropathic symptoms and their impacts on patient s QOL
Study population Cancer patients who plan to receive chemotherapy treatment with either taxane class vinca alkaloid class platinum compounds or bortezomib
Design This is a prospective exploratory natural history study to identify the molecular-genetic mechanisms involved in chemotherapy-induced neuropathy in cancer patients A physician-based neuropathy scale patient neurotoxocity questionnaire and the total neuropathy score will be used to measure the severity of peripheral neuropathy at baseline and after completion of each cycle of chemotherapy infusion Whole peripheral blood and skin biopsy only from patients who consent to biopsies will be collected at baseline and after a subsequent infusion cycle to evaluate geneprotein expression and immunohistochemical labeling at peripheral sites of neuropathic injury Microarray gene expression analysis will be employed to identify differential regulation of genes involved in the development of CIPN at the different time points compared with gene expression from the baseline samples Genes of interest will be validated by qRT-PCR to identify novel pharmacological targets to be evaluated in future prospective studies Protein levels corresponding to the changes in gene expression will be evaluated using ELISA and verified by Western blotting
Outcome measures The primary outcome of the study will be the changes in gene and protein expression in the peripheral blood and skin biopsy among cancer patients undergoing chemotherapy The secondary outcome will be the relationship between the molecular-genetic biomarkers identified and the presence of peripheral neuropathic symptoms and their impacts on patient s QOL
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 |
|---|---|---|---|
| 11-NR-0065 | None | None | None |