Ignite Creation Date:
2024-05-05 @ 5:20 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00431925
Status:
UNKNOWN
Last Update Posted:
2007-08-10
First Post:
2007-02-05
Brief Title:
Can Cytokines Predict the Severity of Acute Mucositis and the Need for Gastrostomy Tubes PEG
Sponsor:
Hadassah Medical Organization
Organization:
Hadassah Medical Organization
Study Overview
Official Title:
Can Cytokines Predict the Severity of Acute Mucositis and the Need for PEG During Chemo-Radiation Treatment to Head and Neck Cancer
Status:
UNKNOWN
Status Verified Date:
2007-02
Last Known Status:
NOT_YET_RECRUITING
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:
Mucositis and xerostomia are the most common complications of head and neck HN irradiation and the combination of chemotherapy and radiation therapy is associated with a significantly higher rate of complications
Mucositis usually develops during the second or third week of a course of standard radiotherapy and the pain it causes peaks between the third and last week of treatment The pain then persists for at least one month following the completion of therapy and may be so overwhelming that it prevents patients from swallowing food and fluids The patient is therefore at a risk to develop malnutrition and must be treated vigorously In this respect the use of gastrostomy tubes PEG has been shown to be beneficial
Completion of the full course of irradiation without interruption is important for achieving best possible results in cancer of the HN It is therefore essential to identify and refer patients at risk to receive effective and timely nutritional intervention
Since mucositis represents a clinical continuum which differs between patients it is difficult to assess before-hand which patients will be at risk
There is no simple laboratory tool available which could predict which patients are susceptible to develop severe mucositis and dysphagia and eventually will require a feeding gastrostomy
The first phase of mucositis inflammation results in the production of pro-inflammatory cytokines such as interleukin-1 IL-1 and tumor necrosis factor-alpha TNF-α
In general the inflammatory cytokines IL-1 interleukin-6 IL-6 and TNF-α are elevated in inflammatory conditions and are found in increased levels in blood and tissue fluid during inflammation while anti-inflammatory cytokines are produced in a decreased manner
The main purpose of this study is to find the best indicators and prognosticators of mucositis occurring in the healthy oral tissues of HN cancer patients receiving treatment and to understand the cytokines balance mechanism of action
Assuming there is a correlation between high cytokines levels during inflammation and the severity of radiation induced mucositis finding these prognostic factors may help us predict during the first part of the treatment the need for PEG placing it prior to the complications associated with severe mucositis on one hand and avoiding unnecessary procedures on the other hand
Mucositis usually develops during the second or third week of a course of standard radiotherapy and the pain it causes peaks between the third and last week of treatment The pain then persists for at least one month following the completion of therapy and may be so overwhelming that it prevents patients from swallowing food and fluids The patient is therefore at a risk to develop malnutrition and must be treated vigorously In this respect the use of gastrostomy tubes PEG has been shown to be beneficial
Completion of the full course of irradiation without interruption is important for achieving best possible results in cancer of the HN It is therefore essential to identify and refer patients at risk to receive effective and timely nutritional intervention
Since mucositis represents a clinical continuum which differs between patients it is difficult to assess before-hand which patients will be at risk
There is no simple laboratory tool available which could predict which patients are susceptible to develop severe mucositis and dysphagia and eventually will require a feeding gastrostomy
The first phase of mucositis inflammation results in the production of pro-inflammatory cytokines such as interleukin-1 IL-1 and tumor necrosis factor-alpha TNF-α
In general the inflammatory cytokines IL-1 interleukin-6 IL-6 and TNF-α are elevated in inflammatory conditions and are found in increased levels in blood and tissue fluid during inflammation while anti-inflammatory cytokines are produced in a decreased manner
The main purpose of this study is to find the best indicators and prognosticators of mucositis occurring in the healthy oral tissues of HN cancer patients receiving treatment and to understand the cytokines balance mechanism of action
Assuming there is a correlation between high cytokines levels during inflammation and the severity of radiation induced mucositis finding these prognostic factors may help us predict during the first part of the treatment the need for PEG placing it prior to the complications associated with severe mucositis on one hand and avoiding unnecessary procedures on the other hand
Detailed Description:
Mucositis has a significant detrimental effect on patients quality of life in terms of pain ability to eat to swallow and talk It may be so severe that an interruption of therapy is required consequently influencing tumor response and overall patient outcome
The degree of mucositis varies between different patients some patients may develop a limited condition confined to patches of mildly sore erythematous mucosa while others may experience diffuse areas of painful ulceration
In the more severe cases pain may be so overwhelming that it prevents patients from swallowing food and fluids The patient is therefore at a risk to develop malnutrition and must be treated vigorously In this respect the use of gastrostomy tubes PEG has been shown to be beneficial
Another aspect of radiation induced mucositis is its health-care costs Patients with more severe mucositis have statistically greater outpatient support costs these include maintenance of appropriate nutritional and hydration support such as placement of gastrostomy tubes In the US the mucositis overall medical costs are in the order of approximately 30001000 per treatment
Completion of the full course of irradiation without interruption is important for achieving best possible results in cancer of the HN It is therefore essential to identify and refer patients at risk to receive effective and timely nutritional intervention
Since mucositis represents a clinical continuum which differs between patients it is difficult to assess before-hand which patients will be at risk to develop severe mucositis during the course of radiotherapy In todays practice patients undergoing radiation therapy of the HN will undergo feeding gastrostomy by the treating physician prior to the treatment if he will anticipate severe mucositis based on the radiation fields the chemotherapy used and his prior experience Some of these procedures were eventually unnecessary In cases where gastrostomy was not placed a priory the common practice is monitoring the patients during treatment If their weight loss exceeds 10 of their initial body weight a feeding gastrostomy is recommended at this time point the mucositis is usually severe and many patients need admission for fluid administration and semi-urgent procedure
Unfortunately there is no simple laboratory tool available which could predict which patients are susceptible to develop severe mucositis and dysphagia and eventually will require a feeding gastrostomy
Mucositis develops in four successive phases an inflammation phase an epithelial phase an ulceration phase and lastly a healing phase
The first phase inflammation is also entitled the initial tissue injury phase and it results in the production of pro-inflammatory cytokines such as IL-1 and TNF-α
In general the inflammatory cytokines IL-1 IL-6 and TNF-α are elevated in inflammatory conditions and are found in increased levels in blood and tissue fluid during inflammation while anti-inflammatory cytokines are produced in a decreased manner
In breast cancer patients it has been shown that changes in cytokines levels Including IL-1β and IL-6 also correspond with the response of the malignant tissue to treatment In this case a good clinical response to therapy has been associated with decreases in IL-1β and IL-6 levels versus increases in their levels which have been associated with the progression of the disease Furthermore tumor markers such as the cytokeratin TPS have been shown to be sensitive in assessing the tumors response to therapy and the patients prognosis
It should be emphasized though that the findings cited above reflect the response of tumor cells to therapy while the proposed project deals with radiation effects on both normal tissues and tumor
The main purpose of this study is to find the best indicators and prognosticators of mucositis occurring in the healthy oral tissues of HN cancer patients receiving treatment and to understand the cytokines balance mechanism of action
Assuming there is a correlation between high cytokines levels during inflammation and the severity of radiation induced mucositis finding these prognostic factors may help us predict during the first part of the treatment the need for PEG placing it prior to the complications associated with severe mucositis on one hand and avoiding unnecessary procedures on the other hand This study may also lead to a new strategy of assessing severity of mucositis by laboratory tests a tool that can be used as an objective assessment in developing strategies that aim to reduce the mucositis The understanding of the cytokines balance in this condition can also be translated to the use of anti-cytokine treatment for this condition similar to other immune related diseases such as RA Crohns Disease and MS
Secondary aims of this study are to measure recently available tumor markers SCC and TPS and to correlate them with tumor response Genetic markers will be assessed for extreme alteration in radiation reactions such as severe skin reaction early and unexpectedly severe mucositis and on the other hand - lack of response The blood for these tasks will be collected prospectively but evaluated at the end of the study
The study will comprise of at least 14 and up to 35 patients with HN epithelial cancer
Patients will be clinically evaluated during the week before treatment and during the treatment period weekly
Blood samples will be drown for cytokines prior to treatment at week 2 4 and at the end of the treatment The serum collected will be separated for the following factors
1 Inflammatory Cytokines IL-1 IL-6 IL-8 IL-18 and TNF α
2 Anti inflammatory cytokines IL-10 and TGF β
3 Tumor markers SCC and TPS
4 Genetic assessment of genes that may be involved in extreme treatment reaction At each weekly follow up patients will be assessed for mucositis by physician using the WHO common toxicity criteria and will answer a mucositis questionnaire based on the RTOGEORTC questionnaire Patients weight will also be recorded
Scientific aims
The primary aims
1 To investigate the relationship between cytokine level and the clinically suggested PEG at the end of the HN chemo-irradiation
2 To investigate whether a correlation exists between blood cytokines inflammatory versus anti-inflammatory cytokines levels and the severity of radiation induced mucositis in patients receiving chemo-radiotherapy for cancer of the HN
3 To investigate whether blood cytokines levels could serve as a simple laboratory tool to predict the severity of mucositis and dysphagia occurring during HN chemo-irradiation
The secondary aims
1 To study the clinical usefulness of the Tumor Markers SCC and TPS in this setting namely to evaluate the correlation between their blood levels and response to therapy
2 To compare the associated mucositis between two commonly used radiation treatment strategies - IMRT 5 field plan and classic two dimensional plan for the subgroup of patients with advanced glottic and supraglottic cancer
3 To assess whether cytokine levels during treatment can predict long term treatment related toxicity
The degree of mucositis varies between different patients some patients may develop a limited condition confined to patches of mildly sore erythematous mucosa while others may experience diffuse areas of painful ulceration
In the more severe cases pain may be so overwhelming that it prevents patients from swallowing food and fluids The patient is therefore at a risk to develop malnutrition and must be treated vigorously In this respect the use of gastrostomy tubes PEG has been shown to be beneficial
Another aspect of radiation induced mucositis is its health-care costs Patients with more severe mucositis have statistically greater outpatient support costs these include maintenance of appropriate nutritional and hydration support such as placement of gastrostomy tubes In the US the mucositis overall medical costs are in the order of approximately 30001000 per treatment
Completion of the full course of irradiation without interruption is important for achieving best possible results in cancer of the HN It is therefore essential to identify and refer patients at risk to receive effective and timely nutritional intervention
Since mucositis represents a clinical continuum which differs between patients it is difficult to assess before-hand which patients will be at risk to develop severe mucositis during the course of radiotherapy In todays practice patients undergoing radiation therapy of the HN will undergo feeding gastrostomy by the treating physician prior to the treatment if he will anticipate severe mucositis based on the radiation fields the chemotherapy used and his prior experience Some of these procedures were eventually unnecessary In cases where gastrostomy was not placed a priory the common practice is monitoring the patients during treatment If their weight loss exceeds 10 of their initial body weight a feeding gastrostomy is recommended at this time point the mucositis is usually severe and many patients need admission for fluid administration and semi-urgent procedure
Unfortunately there is no simple laboratory tool available which could predict which patients are susceptible to develop severe mucositis and dysphagia and eventually will require a feeding gastrostomy
Mucositis develops in four successive phases an inflammation phase an epithelial phase an ulceration phase and lastly a healing phase
The first phase inflammation is also entitled the initial tissue injury phase and it results in the production of pro-inflammatory cytokines such as IL-1 and TNF-α
In general the inflammatory cytokines IL-1 IL-6 and TNF-α are elevated in inflammatory conditions and are found in increased levels in blood and tissue fluid during inflammation while anti-inflammatory cytokines are produced in a decreased manner
In breast cancer patients it has been shown that changes in cytokines levels Including IL-1β and IL-6 also correspond with the response of the malignant tissue to treatment In this case a good clinical response to therapy has been associated with decreases in IL-1β and IL-6 levels versus increases in their levels which have been associated with the progression of the disease Furthermore tumor markers such as the cytokeratin TPS have been shown to be sensitive in assessing the tumors response to therapy and the patients prognosis
It should be emphasized though that the findings cited above reflect the response of tumor cells to therapy while the proposed project deals with radiation effects on both normal tissues and tumor
The main purpose of this study is to find the best indicators and prognosticators of mucositis occurring in the healthy oral tissues of HN cancer patients receiving treatment and to understand the cytokines balance mechanism of action
Assuming there is a correlation between high cytokines levels during inflammation and the severity of radiation induced mucositis finding these prognostic factors may help us predict during the first part of the treatment the need for PEG placing it prior to the complications associated with severe mucositis on one hand and avoiding unnecessary procedures on the other hand This study may also lead to a new strategy of assessing severity of mucositis by laboratory tests a tool that can be used as an objective assessment in developing strategies that aim to reduce the mucositis The understanding of the cytokines balance in this condition can also be translated to the use of anti-cytokine treatment for this condition similar to other immune related diseases such as RA Crohns Disease and MS
Secondary aims of this study are to measure recently available tumor markers SCC and TPS and to correlate them with tumor response Genetic markers will be assessed for extreme alteration in radiation reactions such as severe skin reaction early and unexpectedly severe mucositis and on the other hand - lack of response The blood for these tasks will be collected prospectively but evaluated at the end of the study
The study will comprise of at least 14 and up to 35 patients with HN epithelial cancer
Patients will be clinically evaluated during the week before treatment and during the treatment period weekly
Blood samples will be drown for cytokines prior to treatment at week 2 4 and at the end of the treatment The serum collected will be separated for the following factors
1 Inflammatory Cytokines IL-1 IL-6 IL-8 IL-18 and TNF α
2 Anti inflammatory cytokines IL-10 and TGF β
3 Tumor markers SCC and TPS
4 Genetic assessment of genes that may be involved in extreme treatment reaction At each weekly follow up patients will be assessed for mucositis by physician using the WHO common toxicity criteria and will answer a mucositis questionnaire based on the RTOGEORTC questionnaire Patients weight will also be recorded
Scientific aims
The primary aims
1 To investigate the relationship between cytokine level and the clinically suggested PEG at the end of the HN chemo-irradiation
2 To investigate whether a correlation exists between blood cytokines inflammatory versus anti-inflammatory cytokines levels and the severity of radiation induced mucositis in patients receiving chemo-radiotherapy for cancer of the HN
3 To investigate whether blood cytokines levels could serve as a simple laboratory tool to predict the severity of mucositis and dysphagia occurring during HN chemo-irradiation
The secondary aims
1 To study the clinical usefulness of the Tumor Markers SCC and TPS in this setting namely to evaluate the correlation between their blood levels and response to therapy
2 To compare the associated mucositis between two commonly used radiation treatment strategies - IMRT 5 field plan and classic two dimensional plan for the subgroup of patients with advanced glottic and supraglottic cancer
3 To assess whether cytokine levels during treatment can predict long term treatment related toxicity
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