Study Using Induction Chemotherapy and Intensity-Modulated Radiation Therapy Guided by Combined CT and PET Imaging for Patients With Non-Small Cell Lung Cancer
|First Received Date ICMJE||August 9, 2005|
|Last Updated Date||February 8, 2010|
|Start Date ICMJE||September 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||safety and adverse effects|
|Original Primary Outcome Measures ICMJE
||-safety and adverse effects|
|Change History||Complete list of historical versions of study NCT00128999 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||efficacy and survival|
|Original Secondary Outcome Measures ICMJE
||-efficacy and survival|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study Using Induction Chemotherapy and Intensity-Modulated Radiation Therapy Guided by Combined CT and PET Imaging for Patients With Non-Small Cell Lung Cancer|
|Official Title ICMJE||A Phase I/II 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|
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.
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.
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: 79.5 Gy in 40 fractions over 6 wks; Dose level 3: 75. Gy in 40 fractions over 5 wks.
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 (0/5), 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 (1/5) and no acute DLTs in the last two patients (0/2), 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:
Reporting of SAEs is as follows:
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 Type ICMJE||Interventional|
|Study Phase||Phase 1
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Carcinoma, Non-Small-Cell Lung|
|Intervention ICMJE||Procedure: Intensity-Modulated Radiation Therapy|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||August 2007|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Canada|
|NCT Number ICMJE||NCT00128999|
|Other Study ID Numbers ICMJE||LU-11-0035|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Alberta Health Services|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Alberta Health Services|
|Verification Date||October 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP