Irradiation of Large Lung Tumors or Two or More Lung Metastases Simultaneously

Study Overview
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Brief Summary
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Treatment of larger tumor volumes or ≥ 2 lung metastases simultaneously in lung cancer patient using Stereotactic Body Radiation Therapy (SBRT) in a mean-lung dose escalation study.

Detailed Description
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A phase I/II multicenter trial will be conducted in patients with medically inoperable with peripheral non small cell lung cancer (NSCLC) > 5 cm without lymph node involvement (group A) or medically with ≥ 2 or more lung metastases (group B). Radiation pneumonitis is expected to be dose-limiting in these patients and there is evidence that the incidence is predicted by the mean lung dose (MLD). The MLD escalation will be performed separately in both patient groups, using a time-to-event continual reassessment method (TITE-CRM). All patients will receive 3-5 fractions SBRT to the lung tumor(s), with a minimum mean PTV dose ≥ 42 Gy. Fraction size may be downscaled based on the MLD constraint.

Official Title
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VOLUMES Treatment of Larger Tumor Volumes or ≥ 2 Lung Tumors Simultaneously in Lung Cancer Patients Using SBRT in a Mean-lung Dose Escalation Study

Conditions
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Lung Cancer, Metastatic Lung Cancer

Intervention / Treatment
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* Radiation: Stereotactic Body Radiotherapy (SBRT)
* Radiation: Stereotactic Body Radiotherapy (SBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for group A and B: Weight loss < 10% in the last three months. WHO-performance status ≤ 2 Medical inoperable patients or patients refusing surgery. Chemotherapy is allowed in neoadjuvant and adjuvant setting, with exclusion of the period 4 weeks pre-SBRT and 6 weeks post-SBRT. Before patient registration, written informed consent must be given according to ICH/GCP, national and local regulations. Risk group A specification: NSCLC (Cytological or histological proven) patients with peripheral tumors >5 cm with tumor staging cT2bN0M0 or cT3N0M0 (chest wall infiltration is no exclusion criteria, as long as the tumor diameter is > 5 cm). Single peripheral lung metastasis in inoperable patients with a diameter of > 5 cm. In case of first presentation of metastatic disease, cytological or histological proof is obligated. In patients without cytological or histological confirmation of NSCLC, a growing FDG-PET positive lesion (SUV >5) is accepted if a contra-indication for invasive diagnostic examination (or refusal) is present. Risk group B specification: Patients with ≥ 2 simultaneous peripheral lung metastases ≤ 5 cm of any origin at any location in the lung. In case of first presentation of metastatic disease, cytological or histological proof is obligated. This is not necessary in case of a history of an already proven disseminated disease. Patients having ≥ 2 peripheral lung metastases without unacceptable dose overlap. Exclusion Criteria: Patients with central tumors Pancoast tumors Prior radiotherapy treatment to the thorax Patients receiving any systemic treatment during SBRT Pregnant patients Patients previously treated with adriamycin agents in case of heart involvement within the treatment field.

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: SBRT group A<br>escalate MLD in medically inoperable patients with tumors larger than 5 cm in diameter (primary or solitary metastases) | Radiation: Stereotactic Body Radiotherapy (SBRT)<br>* 3-5 fractions within 10-14 days<br>* Other names: Stereotactic Body Radiotherapy;|
| Experimental: SBRT group B<br>Escalate the MLD in patients with ≥ 2 lung metastases | Radiation: Stereotactic Body Radiotherapy (SBRT)<br>* 3-5 fractions per tumor within one treatment session or sequential within one month<br>* Other names: Stereotactic Body Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MLD | The assessment of the maximum mean lung dose that can be safely treated with SBRT and that is associated with a 20% probability of the DLT. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| loco-regional control | Determine the local control and regional control as a function of the mean lung dose, the largest toxicity effects as a function of the MLD and the overall survival. | 4 years | 
| overall survival | Determine the local control and regional control as a function of the mean lung dose, the largest toxicity effects as a function of the MLD and the overall survival. | 5 years | 
| Quality of life assessment | valuate the increase or decrease of physical discomfort. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung, SBRT, MLD, toxicity