Ignite Creation Date:
2024-05-05 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00128999
Status:
COMPLETED
Last Update Posted:
2010-02-09
First Post:
2005-08-09
Brief Title:
Study Using Induction Chemotherapy and Intensity-Modulated Radiation Therapy Guided by Combined CT and PET Imaging for Patients With Non-Small Cell Lung Cancer
Sponsor:
Alberta Health services
Organization:
AHS Cancer Control Alberta
Study Overview
Official Title:
A Phase III Dose Escalation Study Using Induction Chemotherapy and Intensity-Modulated Radiation Therapy Guided by Combined CT and PET Imaging for Patients With Non-Small Cell Lung Cancer
Status:
COMPLETED
Status Verified Date:
2007-10
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:
Lung cancer is the leading cause of cancer-related mortality in the United States US and Canada Because of the high incidence and mortality of this disease small improvements in the management of this disease translates into large numbers of patients having improved outcomes after treatment Radiation therapy is widely used to treat patients with lung cancer However the radiation dose to the tumor has been limited by the proximity of normal structures to the tumor such as the lung the spinal cord and the esophagus The normal structures must not be exposed to excessive radiation doses A new technique called intensity-modulated radiotherapy delivers radiation to tumors such that the normal structures around the tumor are exposed to less radiation than previously achievable This technique is already used to treat head and neck cancers This study will use this technique to deliver more intensified radiation to the lung tumor after the patient receives two cycles of chemotherapy A new imaging technique called positron emission tomography PET has been found to be more sensitive and specific at detecting the extent of the tumor in the lung than the older imaging technique of computed tomography CT This study will use both the PET and CT to target the radiation beams Following treatment the patients will be followed up to assess the side effects of normal tissues and response of the tumor to the treatment
Detailed Description:
Hypothesis and Objectives The hypothesis that respiratory gated IMRT can escalate safely radiation doses for NSCLC with induction chemotherapy will be tested The intent of the study is to determine the maximum tolerable dose of radiotherapy for NSCLC using a novel treatment planning technique with accelerated fractionation given with state-of-the-art imaging guidance
Primary Objective
To establish the maximum tolerated dose of radiotherapy by assessing treatment toxicity according to the acute RTOG grading scale
Secondary Objectives
To evaluate the treatment toxicity of the combination regimen according to the chronic RTOG grading scale
Quality of Life to be assessed using the EORTC QLQ-C30 and LC13
To determine progression-free survival with this regimen
To identify partial organ tolerance doses for lung esophagus and heart
Schema and Methods Eligible patients who have consented will receive two cycles of cisplatin-vinorelbine chemotherapy Thoracic radiotherapy will be given afterwards according to the dose-escalating scale Only one dose level will open at one time Dose level 1 84 Gy in 35 fractions over 7 wks Dose level 2 795 Gy in 40 fractions over 6 wks Dose level 3 75 Gy in 40 fractions over 5 wks
Eligibility Criteria
Patients with histologically-proven by biopsy or cytology unresected NSCLC
Patients with AJC Stage I-III if all detectable tumors can be encompassed by radiation therapy fields
Patients with positive supraclavicular node N3 or malignant pleural effusion are not eligible
Age 18
Karnofsky performance status 70
ANC 15 Plt 100000 Hct 30 AST SGOT 15 ULN serum creatinine 15 mgdL
Patients must have measurable disease on the CT and PET images
Patients must have a FEV1 10 L
Evaluation of the total lung volume receiving 20 Gy V20 must be 30 mean esophageal dose must be 32 Gy and the esophageal V 55 28
Patients must have a satisfactory IMRT plan prior to start of radiotherapy
Statistical Considerations
Primary Endpoint The frequency of patients developing unacceptable grade 3 or higher toxicity according to the RTOG acute toxicity scale attributable to radiotherapy Acute radiotherapy toxicities are defined as those toxicities that occur within 90 days from the start of radiotherapy
Sample Size In order to establish the maximum tolerated dose MTD of radiotherapy that can be delivered using IMRT following induction chemotherapy acceptable morbidity criteria must be defined Based on the Radiation Therapy Oncology Group RTOG 94-10 the dose limiting toxicity DLT defined as a grade 3 or 4 non-hematologic toxicity rate for this study is determined to be 40 After 7 evaluable patients have been followed for a minimum of 90 days from the start of radiation therapy patients will be evaluated with respect to treatment morbidity If there are no acute dose limiting toxicities in the first 5 patients 05 then the current dose will be deemed to be acceptable and will be escalated If there is 1 acute DLT observed in the first 5 patients 15 and no acute DLTs in the last two patients 02 then the dose will be deemed to be acceptable and will be escalated Otherwise the current dose will be deemed to be too toxic and escalation will end This design gives at least 90 confidence that the true acute DLT rate at a given dose level is less than 40 and for any given dose level the probability of not escalating when the true toxicity rate is 40 or higher is at least 88
Safety Monitoring and Stoppage Rules An SAE is any untoward medical occurrence that
results in death
is life-threatening patient is at immediate risk of death
requires inpatient hospitalization or prolongation of existing hospitalization
results in persistent or significant disabilityincapacity
is congenital anomalybirth defect
important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed in this definition
Reporting of SAEs is as follows
1 Complete the Serious Adverse Event Report
2 Fax the Serious Adverse Event Report within 24 hours of the investigators or designees knowledge of the event to the attention of Dr Wilson Roa 780 432-8517 tel780 432-8380 fax and Dr Don Yee 403 944-2895 tel403 283-1651 fax
3 Accrual may be stopped immediately as indicated upon review and confirmation of the SAE by the two PIs
Recruitment and Reporting The projection rate of accrual was based on a previous preliminary study At this rate it would take three months to complete accrual for each of the 3 dose levels A three-month waiting period is required prior to dose escalation to the next level Hence an estimate of 7 months is conservatively allowed for each level amounting to a total of 21 months to complete accrual treatments and waiting period for the primary endpoint The first manuscript on this study will be completed by the end of two years Analysis for the reporting treatment results will contain tabulation of all cases entered and any excluded from analysis with reasons for the exclusion Respective institutional accrual and observed endpoints of MTD toxicity progression-free survival and quality of life will be analyzed
Primary Objective
To establish the maximum tolerated dose of radiotherapy by assessing treatment toxicity according to the acute RTOG grading scale
Secondary Objectives
To evaluate the treatment toxicity of the combination regimen according to the chronic RTOG grading scale
Quality of Life to be assessed using the EORTC QLQ-C30 and LC13
To determine progression-free survival with this regimen
To identify partial organ tolerance doses for lung esophagus and heart
Schema and Methods Eligible patients who have consented will receive two cycles of cisplatin-vinorelbine chemotherapy Thoracic radiotherapy will be given afterwards according to the dose-escalating scale Only one dose level will open at one time Dose level 1 84 Gy in 35 fractions over 7 wks Dose level 2 795 Gy in 40 fractions over 6 wks Dose level 3 75 Gy in 40 fractions over 5 wks
Eligibility Criteria
Patients with histologically-proven by biopsy or cytology unresected NSCLC
Patients with AJC Stage I-III if all detectable tumors can be encompassed by radiation therapy fields
Patients with positive supraclavicular node N3 or malignant pleural effusion are not eligible
Age 18
Karnofsky performance status 70
ANC 15 Plt 100000 Hct 30 AST SGOT 15 ULN serum creatinine 15 mgdL
Patients must have measurable disease on the CT and PET images
Patients must have a FEV1 10 L
Evaluation of the total lung volume receiving 20 Gy V20 must be 30 mean esophageal dose must be 32 Gy and the esophageal V 55 28
Patients must have a satisfactory IMRT plan prior to start of radiotherapy
Statistical Considerations
Primary Endpoint The frequency of patients developing unacceptable grade 3 or higher toxicity according to the RTOG acute toxicity scale attributable to radiotherapy Acute radiotherapy toxicities are defined as those toxicities that occur within 90 days from the start of radiotherapy
Sample Size In order to establish the maximum tolerated dose MTD of radiotherapy that can be delivered using IMRT following induction chemotherapy acceptable morbidity criteria must be defined Based on the Radiation Therapy Oncology Group RTOG 94-10 the dose limiting toxicity DLT defined as a grade 3 or 4 non-hematologic toxicity rate for this study is determined to be 40 After 7 evaluable patients have been followed for a minimum of 90 days from the start of radiation therapy patients will be evaluated with respect to treatment morbidity If there are no acute dose limiting toxicities in the first 5 patients 05 then the current dose will be deemed to be acceptable and will be escalated If there is 1 acute DLT observed in the first 5 patients 15 and no acute DLTs in the last two patients 02 then the dose will be deemed to be acceptable and will be escalated Otherwise the current dose will be deemed to be too toxic and escalation will end This design gives at least 90 confidence that the true acute DLT rate at a given dose level is less than 40 and for any given dose level the probability of not escalating when the true toxicity rate is 40 or higher is at least 88
Safety Monitoring and Stoppage Rules An SAE is any untoward medical occurrence that
results in death
is life-threatening patient is at immediate risk of death
requires inpatient hospitalization or prolongation of existing hospitalization
results in persistent or significant disabilityincapacity
is congenital anomalybirth defect
important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed in this definition
Reporting of SAEs is as follows
1 Complete the Serious Adverse Event Report
2 Fax the Serious Adverse Event Report within 24 hours of the investigators or designees knowledge of the event to the attention of Dr Wilson Roa 780 432-8517 tel780 432-8380 fax and Dr Don Yee 403 944-2895 tel403 283-1651 fax
3 Accrual may be stopped immediately as indicated upon review and confirmation of the SAE by the two PIs
Recruitment and Reporting The projection rate of accrual was based on a previous preliminary study At this rate it would take three months to complete accrual for each of the 3 dose levels A three-month waiting period is required prior to dose escalation to the next level Hence an estimate of 7 months is conservatively allowed for each level amounting to a total of 21 months to complete accrual treatments and waiting period for the primary endpoint The first manuscript on this study will be completed by the end of two years Analysis for the reporting treatment results will contain tabulation of all cases entered and any excluded from analysis with reasons for the exclusion Respective institutional accrual and observed endpoints of MTD toxicity progression-free survival and quality of life will be analyzed
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