Phase I Hypofractionated Stereotactic Boost (Radiotherapy) for Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This study will help researchers test the safety of hypofractionated dose of radiotherapy (HySBst) at different dose levels before or after chemo-radiation for Non Small Cell Lung Cancer.

Detailed Description
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Patients are assigned to Sub-group 1 or 2 based on the primary lesion size and location. This protocol will utilize a standard 3 + 3 phase I design with three patients enrolled per cohort. Patients will be offered the opportunity to participate in the blood specimen component of the study. Patients will be followed up to 2 years post radiation therapy. Sub-group 1 will receive HySBst for 1 week. Weeks 2-7 will be standard chemo-radiation therapy. Patients have the option of consolidative chemotherapy at week 12. Sub-group 2 will receive standard chemo-radiation therapy for weeks 1-6 then receive HySBst during week 7. Patients have the option of consolidative chemotherapy at week 12. HySBst dose escalation for each sub-group is listed below: Optional: 4 Gy x 4 daily fractions Level 1: 5 Gy x 4 daily fractions Level 2: 5.5 Gy x 4 daily fractions Level 3: 6 Gy x 4 daily fractions DLTs will be based on events occurring during the course of HySBst. Chemo-Radiation Therapy is defined as: Standard Carboplatin & Paclitaxel Doublelet Regimen with weekly Carboplatin AUC 2/week and Paclitaxel 45 mg/ m2/ week during conventionally fractionated IMRT Image-guided IMRT to 60 Gy, 5 x per week for 6 weeks Consolidative chemotherapy is defined as Carboplatin AUC 6 and Paclitaxel 200 mg/m2 every 21 days x 2 cycles will be given after ALL radiotherapy is delivered.

Official Title
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Phase I Dose Escalation Study of a Hypofractionated Stereotactic Boost (HySBst) to the Primary Site in Patients With Stage II-III Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Hypofractionated Stereotactic Boost
* Drug: Carboplatin
* Drug: Paclitaxel
* Radiation: Image-guided IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage II - III Non Small Cell Lung Cancer Exclusion Criteria: Primary tumor directly invading into any mediastinal structures, such as the heart, major blood vessels, esophagus, trachea, and the proximal bronchial tree. Prior chemotherapy for NSCLC Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields. Severe, active co-morbidity Pregnancy or women of childbearing potential Any history of allergic reaction to paclitaxel or other taxanes, or to carboplatin Uncontrolled neuropathy ≥ grade 2.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sub-group 1<br>HySBst to be delivered during week 1 with Chemo-radiation to be delivered weeks 2-7 | Radiation: Hypofractionated Stereotactic Boost<br>* An ablative dose of radiation is delivered to the primary tumor target over a week through Stereotactic Ablative Radiotherapy.<br>* Other names: HySBst;Drug: Carboplatin<br>* Given during chemo-radiation phase and optional consolidative phase.<br>Drug: Paclitaxel<br>* Given during chemo-radiation phase and optional consolidative phase.<br>Radiation: Image-guided IMRT<br>* Given during chemo-radiation phase<br>|
| Experimental: Sub-group 2<br>Chemo-radiation to be delivered weeks 1-6 and HySBst to be delivered week 7 | Radiation: Hypofractionated Stereotactic Boost<br>* An ablative dose of radiation is delivered to the primary tumor target over a week through Stereotactic Ablative Radiotherapy.<br>* Other names: HySBst;Drug: Carboplatin<br>* Given during chemo-radiation phase and optional consolidative phase.<br>Drug: Paclitaxel<br>* Given during chemo-radiation phase and optional consolidative phase.<br>Radiation: Image-guided IMRT<br>* Given during chemo-radiation phase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose of HySBst |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity |  | 1 week | 
| Blood Sample Collection | Biomarker analysis | 2 years | 
| Local Control | To determine the 2-year regional, and distant metastasis rates, progression-free survival (PFS), local progression free survival (L-PFS), overall survival (OS) | 2 years | 
| Quality of Life | To determine the quality of life before and after treatment using the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 and Lung Cancer 13 (EORTC QLQ-C30, and the LC 13) scales | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small Cell Lung Cancer, Radiotherapy Therapy