Phase I Study of Accelerated Hypofractionated Image-Guided Radiation Therapy

Study Overview
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Brief Summary
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The study is designed to determine whether daily image guidance and motion assessment/control will allow treatment of poor performance status patients with stage II-IV NSCLC, who would benefit from local therapy, with an accelerated course of hypofractionated radiation therapy.

Detailed Description
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Subjects for this study will be enrolled by the Moncrief Radiation oncology Department at the Simmons Cancer Center. Primary objective: To escalate the dose of accelerated, hypofractionated, image-guided conformal radiotherapy to a potent tumorcidal dose without exceeding the maximum tolerated dose in treatment of stage ii-iV nSCLC in patients with poor performance status. Secondary objectives: To evaluate local regional tumor control and overall survival in patients with stage ii-iV nSCLC and poor performance status treated with accelerated, hypofractionated, image-guided conformal radiotherapy. Schema number of patients between 7-45 (depending on tolerance) Patients in each dose cohort will all be treated as a single group for dose escalation. The starting dose will be 3.33 Gy per fraction for 15 fractions (total dose 50 Gy). Subsequent cohorts of patients will receive a higher dose per fraction as follows: Cohort No. Fractions Dose per fraction (Gy) Total Dose (Gy) No. Patients 15 3.33 50 7-15 15 3.67 55 7-15 15 4.00 60 7-15 Minimum waiting periods will be assigned between each dose cohort to observe toxicity. Screening Procedures each study participant will have the following exams, tests or procedure to help determine if they are qualified to be in this study: Within 8 weeks of enrollment : Computed tomographic (CT) with contrast of the lung and upper abdomen. a CT done in conjunction with a Positron emission Tomography (PeT) scan is satisfactory as long as the images are of adequate quality to be interpreted by a radiologist. an MRi of the brain with contrast (or CT if MRi is medically contraindicated). Complete Blood Count (CBC) with differential Charleston Comorbidity index completion Within 3 days prior to radiotherapy: urine or serum pregnancy test in females of child-bearing capacity. Within 12 weeks of enrollment: * Pulmonary function tests including spirometry for forced expiratory volume in 1 second (FeV-1), diffusing capacity (DLCo), and arterial blood gas (Pao-2). Prior to enrollment on the study: Tissue biopsy or cytology confirming non-small cell lung cancer. Treatment Protocol treatment must begin within 4 weeks after patient registration to the trial. Patients will receive 15 fractions of radiation. Total dose will depend on the dose cohort of the study (see schema). The starting dose level will be 3.33 Gy per fraction for 15 fractions (total dose [?] 50 Gy). Patients must not receive other concomitant antineoplastic therapy (including standard fractionated radiotherapy to the chest, chemotherapy, biological therapy, vaccine therapy, and surgery) within a week prior to, during, or within one week after completing hypofractionated image-guided radiation therapy on protocol. Follow-up Patients will be followed until death.

Official Title
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Phase I Study of Accelerated Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-IV Non-Small Cell Lung Cancer and Poor Performance Status

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Image-Guided Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must be willing and capable to provide informed consent to participate in the protocol. Patients must have appropriate staging studies identifying them as AJCC stage II, III or IV non small cell lung cancer, [according to AJCC Staging, 6th edition; see appendix III], or recurrent non small cell lung cancer. Histologic confirmation of cancer will be required by biopsy or cytology. Patients must have the potential for benefit from local therapy (at the discretion of the investigator). Patient must have a Zubrod performance status of 2 or greater Or Patient must have had >10% weight loss in the past 6 months Or Patient is not eligible for concurrent chemoradiation as determined by a Medical Oncologist and Radiation Oncologist Age ≥ 18. The tumor must be ineligible for definitive surgical resection. The tumor must be ineligible for stereotactic body radiation therapy. Patients must have measurable or evaluable disease. Women of childbearing potential and male participants must agree to use an effective method of contraception. Patients must sign study specific informed consent prior to study entry. Patients must complete all required pretreatment evaluations Exclusion Criteria: Evidence of small cell histology. Tumor eligible for definitive surgical resection. Tumor eligible for definitive stereotactic body radiation therapy. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields. Chemotherapy given within one week of study registration. Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level A: IGRT 3.33Gy x 15 Fractions<br>Image-guided radiation therapy (IGRT) dose of 3.33Gy for 15 fractions (total dose = 50 Gy) which is given over the course of about 3 weeks | Radiation: Image-Guided Radiation Therapy<br>* Radiotherapy to a potent tumorcidal dose<br>|
| Experimental: Dose Level B: IGRT 3.67Gy x 15 Fractions<br>Image-guided radiation therapy (IGRT) dose of 3.67Gy for 15 fractions (total dose = 55 Gy) which is given over the course of about 3 weeks | Radiation: Image-Guided Radiation Therapy<br>* Radiotherapy to a potent tumorcidal dose<br>|
| Experimental: Dose Level C: IGRT 4.00Gy x 15 Fractions<br>Image-guided radiation therapy (IGRT) dose of 3.67Gy for 15 fractions (total dose = 60 Gy) which is given over the course of about 3 weeks | Radiation: Image-Guided Radiation Therapy<br>* Radiotherapy to a potent tumorcidal dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicity | A dose limiting toxicity (DLT) is defined as treatment-related (definitely and probably, but not possibly related to treatment*) grade 3 adverse events (per CTCAE, v.3.0, with the exception of pulmonary function tests) | 90 days after start of treatment up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Local Regional Tumor Control at 3 Months | Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions. | 3 months | 
| Number of Participants With Local Regional Tumor Control at 6 Months | Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions. | 6 months | 
| Number of Participants With Local Regional Tumor Control at 9 Months | Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions. | 9 months | 
| Number of Participants With Local Regional Tumor Control at 12 Months | Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions. | 12 months | 
| Number of Participants With Local Regional Tumor Control at 16 Months | Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions. | 16 months | 
| Number of Participants With Local Regional Tumor Control at 20 Months | Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions. | 20 months | 
| Overall Survival at 6 Months | Overall survival is defined as participants alive during the research period. | 6 months |