Feasibility Study of FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases

Study Overview
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Brief Summary
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This purpose of this study is to assess the feasibility of FLASH radiotherapy for the palliative treatment of painful bone metastases. FLASH radiotherapy is radiation treatment delivered at ultra-high dose rates compared to conventional radiation treatment.

Detailed Description
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This clinical investigation is designed to assess the workflow feasibility of FLASH radiotherapy treatment in a clinical setting, as well as the toxicities, and pain relief when used to treat bone metastasis(-es) in the extremities (excluding feet, hands, wrists). FLASH radiotherapy has been shown in preclinical studies to cause less injury to surrounding normal tissues during radiation treatment, while still having similar tumor cell killing. Patients at least 18 years of age with painful bone metastases located in the limbs will be considered for the study. These patients represent an ideal population for a feasibility study of FLASH radiotherapy as they are known to benefit from the palliative effects of radiotherapy using single dose radiation regimens of 8Gy which is what is being used in this investigation. After treatment, patients will be assessed for pain response as well as any adverse side-effects of radiation. The workflow feasibility of the treatment will also be evaluated.

Official Title
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Feasibility Study of FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases

Conditions
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Bone Metastasis

Intervention / Treatment
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* Radiation: FLASH Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age at least 18 years Up to 3 painful bone metastasis(-es) in the extremities Bone metastases that can be treated using pre-defined treatment field sizes (7.5 cm x 7.5 cm; 7.5 cm x 10 cm; 7.5 cm x 12 cm; 7.5 cm x 14 cm; 7.5 cm x 16 cm; 7.5 cm x 18 cm; 7.5 cm x 20 cm), without overlap of radiation fields Life expectancy of >2 months (in the judgement of the investigator) Patients who are able to comply with the protocol Provision of signed and dated informed consent form Exclusion Criteria: Prior radiotherapy to the treatment site(s) Lesions of the feet, hands, wrists are not eligible treatment sites for FLASH More than 3 painful bone metastases of the limbs requiring palliative radiotherapy Tumor lysis of >50% of the circumferential bone cortex, or other factors considered to place the subject at significant risk of pathologic fracture Patients with bone fractures and/or metal implants in the treatment field Patients who will receive cytotoxic chemotherapy within 1 week prior to or 1 week following their planned radiation treatment Prior local therapy modality to the treatment site(s) within 2 weeks of study enrollment Patients with pacemakers or other implanted devices at risk of malfunction during radiotherapy Patients with any other medical condition or laboratory value that would, at the discretion of the investigator, preclude the patient from participation in this clinical investigation Patients at known risk of enhanced normal tissue sensitivity to radiotherapy due to inherited predisposition or documented comorbidity that might lead to hypersensitivity to ionizing radiation Patients enrolled in any other clinical studies the investigator believes to be in conflict with this clinical investigation. Patients who are pregnant or nursing

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
Intervention Model: Single Group Assignment
Interventional Model Description: Open label, single arm prospective feasibility study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FLASH radiotherapy for painful bone metastasis(-es)<br> | Radiation: FLASH Radiotherapy<br>* FLASH radiotherapy is radiation treatment delivered at ultra-high dose rates compared to conventional radiation treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Workflow feasibility | Treatment for an individual subject will be deemed NOT feasible if total treatment time on table is greater than one hour . | Will be assessed on day of treatment delivery which occurs within 3 weeks of subject enrollment. | 
| Workflow feasibility | Treatment for an individual subject will be deemed NOT feasible if delays in study treatment of more than 7 business days from simulation to treatment occurs related to the investigational device (excluding delays due to patient or facility factors not related to study treatment) | Will be assessed within 4 weeks of subject enrollment. | 
| Assessment of radiation-related toxicities that are possibly, probably, or definitely related to FLASH radiotherapy. | Toxicities that are possibly, probably, or definitely related to FLASH radiotherapy. Toxicities will be classified per CTCAE version 5.0. | Assessed from start of treatment until subject death or lost to follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain relief | Patient reported pain score overall and specifically for treated sites. | Assessed at Day 15, Months 1, 2, 3, long term; flare in bone pain assessed during the first 10 days after treatment | 
| Use of pain medication. | Use of pain medication. | Assessed at baseline and for the first 10 days after treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FLASH radiotherapy, Radiation treatment, Proton, Bone metastasis, Feasibility study, Pain relief, Toxicities, Extremities