Clinical trial NCT04592887: Feasibility Study of FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases
Official title: Feasibility Study of FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bone Metastasis
Keywords: FLASH radiotherapy
Radiation treatment
Proton
Bone metastasis
Feasibility study
Pain relief
Toxicities
Extremities
Lead sponsor: Varian, a Siemens Healthineers Company
Sponsor class: INDUSTRY
First posted: 2020-10-19
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label, single arm prospective feasibility study
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Workflow Feasibility
timeFrame: Will be assessed on day of treatment delivery which occurs within 3 weeks of subject enrollment.
measure: Workflow Feasibility
timeFrame: Will be assessed within 4 weeks of subject enrollment.
measure: Assessment of Radiation-related Toxicities That Are Possibly, Probably, or Definitely Related to FLASH Radiotherapy.
timeFrame: Assessed from start of treatment until subject death or lost to follow-up, up to 17.8 months
Secondary outcomes:
measure: Pain Relief
timeFrame: At 3 month follow up
measure: Number of Participants Who Experienced a Pain Flare.
timeFrame: First 10 days post FLASH treatment
measure: Number of Participants With Increased Use of Pain Medication in First 10 Days Post FLASH Treatment
timeFrame: Within 10 days after treatment.
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Proton Therapy Center
state: Ohio
Study officials:
affiliation: Professor of Radiation Oncology and Neurosurgery, UCMC
name: John Breneman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mascia AE, Daugherty EC, Zhang Y, Lee E, Xiao Z, Sertorio M, Woo J, Backus LR, McDonald JM, McCann C, Russell K, Levine L, Sharma RA, Khuntia D, Bradley JD, Simone CB 2nd, Perentesis JP, Breneman JC. Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases: The FAST-01 Nonrandomized Trial. JAMA Oncol. 2023 Jan 1;9(1):62-69. doi: 10.1001/jamaoncol.2022.5843.
citation: Daugherty EC, Mascia A, Zhang Y, Lee E, Xiao Z, Sertorio M, Woo J, McCann C, Russell K, Levine L, Sharma R, Khuntia D, Bradley J, Simone CB 2nd, Perentesis J, Breneman J. FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases (FAST-01): Protocol for the First Prospective Feasibility Study. JMIR Res Protoc. 2023 Jan 5;12:e41812. doi: 10.2196/41812.
citation: Maity A, Koumenis C. Shining a FLASHlight on Ultrahigh Dose-Rate Radiation and Possible Late Toxicity. Clin Cancer Res. 2022 Sep 1;28(17):3636-3638. doi: 10.1158/1078-0432.CCR-22-1255.