Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Nerve Damage
| Status: | Terminated |
|---|---|
| Conditions: | Cancer, Cancer, Neurology |
| Therapuetic Areas: | Neurology, Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/6/2019 |
| Start Date: | December 22, 2010 |
| End Date: | November 13, 2012 |
Characterization of the Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Peripheral Neuropathy Progression
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....
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 gene/protein 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.
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 gene/protein 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.
- INCLUSION CRITERIA:
Patients must meet all of the following to be eligible for enrollment:
- Age: 18 years and older
- Both male and female cancer patients will be recruited in this study. However, data
will be separately assessed between males and females due to the differences in
incidence, etiology and hormonal dependence which may confound the final data
analyses.
- Ability to provide informed consent
- Cancer patients scheduled to undergo chemotherapy with taxane class, vinca alkaloid
class, platinum compounds or bortezomib
EXCLUSION CRITERIA:
- Patients with any one of the following will be excluded:
- Unable to provide their own informed consent
- Have had prior radiotherapy
- Pre-existing documented neuropathy or risk factors for neuropathy that may confound
the analysis of factors associated with CIPN such as:
- Diabetes mellitus
- Uremia
- Vitamin B12 deficiency
- Peripheral vascular disease
- Documented Thyroid dysfunction with on-going treatment. The patients who have thyroid
dysfunction may also manifest the peripheral neuropathic symptoms such as numbness and
tingling on their feet and hands. The medications used to treat hypothyroidism may
confound the study data assessment.
- Previous history of alcoholism (beriberi) or drug abuse
- Rheumatoid arthritis
- Lupus
- Amyloidosis
- Sarcoidosis
- Other drug-induced neuropathy that may confound the analysis associated with CIPN such
as:
- Thalidomide
- Isoniazid
- Trichloroethylene
- Hydralazine
- Disulfiram
- Nitrofurantoin
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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