Performance and Safety of Biology-Guided Radiotherapy Using the RefleXion Medical Radiotherapy System (BIOGUIDE-X)

NCT04788147 | Completed Results FDA Device

• 1 other identifier: 985-00001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the performance and safety of Biology-Guided Radiotherapy (BgRT) using the RefleXion Medical Radiotherapy System (RMRS) via optimizing F18-Fluorodeoxyglucose (FDG) dosing, assessing the performance of the Positron Emission Tomography (PET) imaging subsystem for BgRT treatment planning and delivery, including its role as an interlock, and validating the dose delivery performance of the end-to-end BgRT workflow.

Conditions

Cancer; Tumor, Solid; Cancer, Lung; Cancer, Bone; Metastasis to Lung; Metastasis to Bone

Keywords

Radiation Oncology; Radiotherapy; Biology-Guided Radiotherapy (BgRT); RefleXion Medical; Radiation Therapy

Outcome Measures

Primary Outcomes (2)

• Cohort I Recommended RefleXion FDG Dose (RRFD) to Enable the Use of BgRT Planning.

  The primary endpoint determined the number of cases that received the lowest FDG dose of 15 mCi, completed the RMRS image session and established an adequate target activity concentration to enable Biology guided Radiotherapy planning. The starting dose was 15mCi which was determined based upon preliminary physics studies done prior to this study. A FDG dose escalation to 20 mCi was not required.

  During the RMRS imaging session

• Cohort II: Delivery Emulation

  The number of scans/fractions where the emulated BgRT dose distribution in a phantom was consistent with the BgRT treatment plan (i.e., 95% of DVH Delivered points for the BTZ and OAR fall within bounded DVH of the approved BgRT plan). There were 9 first fractions and 8 last fractions that were analyzed.

  After SBRT First Fraction (standard of care) and after SBRT Last Fraction (standard of care)

Secondary Outcomes (10)

• Cohort I: Endpoint 1 Percent Agreement Between SI and AS for BgRT PET Imaging-only Session

  Immediately after RMRS imaging session

• Cohort I Endpoint 2: Percent of Cases X1 PET vs. Third-party Diagnostic PET/CT Image Comparison

  Immediately after RMRS imaging session

• Cohort I Endpoint 3: Biology Guided Radiotherapy (BgRT) Plan Generation

  Immediately after RMRS imaging session

• Cohort I Endpoint 4: Percent of Cases Where the Intended Dose Distribution of BgRT Plan Was Achieved in the Physical Phantom.

  Immediately after RMRS imaging session

• Cohort II Endpoint 1 Percent of Fractions With Concordance Between Physical and Digital Phantoms

  Assessed after SBRT First Fraction (standard of care) and after SBRT Last Fraction (standard of care), reported after SBRT Last Fraction.

Study Arms (2)

Cohort I: RRFD Cohort

EXPERIMENTAL

Cohort I seeks to identify the Recommended RefleXion FDG dose (RRFD), which is the dose of administered FDG that allows for functioning of the RefleXion system. This phase of the investigation seeks to optimize the balance between minimizing patient exposure to the radiotracer and achieving satisfactory performance of the RMRS PET subsystem for BgRT. The dose levels of 15 mCi and 20 mCi (if required) will be assessed sequentially in an escalation protocol. To determine the RRFD, a modified 3+3 design will be utilized wherein meeting the Activity Concentration threshold - not dose-limiting toxicity as is typically used - will be the relevant criteria for escalating from one dose to the next. Up to 12 participants will be enrolled in Cohort I, and will undergo one RMRS imaging session and one third-party Positron Emission Tomography (PET) /CT imaging session.

Device: RMRS IDE Device

Cohort II: Emulated Delivery Cohort

EXPERIMENTAL

After the RRFD is determined by Cohort I, Cohort II enrollment will start enrollment. Cohort II seeks to determine whether BgRT dose distributions generated from Limited Time Sample (LTS) RMRS PET images obtained at the time of treatment delivery are consistent with the approved BgRT plan. To achieve this objective, RMRS PET scans will be added to the SBRT workflow at timepoints representing some of the instances when the RMRS PET subsystem would be utilized during a BgRT workflow. Specifically, subjects will undergo RMRS PET collections at the time of planning, and then before the first and final fractions of their planned course of SBRT treatment. Up to 22 participants will be enrolled in Cohort II, and will undergo three RMRS imaging sessions and one third-party Positron Emission Tomography (PET) /CT imaging session.

Device: RMRS IDE Device

Interventions

RMRS IDE Device DEVICE

Participants will be injected with FDG at the studied dose and will undergo imaging sessions using the RMRS IDE device and a third-party Positron Emission Tomography (PET)/CT imaging device.

Also known as: RefleXion Medical, Biology-Guided Radiotherapy (BgRT)

Cohort I: RRFD Cohort; Cohort II: Emulated Delivery Cohort

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than 21 years
• A new or prior diagnosis of biopsy-proven cancer with a solid tumor (non-hematologic, non-lymphoma)
• At least one active tumor in the bone or lung which is either the primary tumor or metastatic lesion determined either by biopsy or imaging suspicious of active disease
• Target tumor size ≥2cm and ≤5cm
• Target lesion in the bone or lung that is discrete and assessed by the investigator to be FDG-avid (i.e. SUVmax≥6 on third-party diagnostic PET/CT performed within 60 days with no intervening oncologic therapies)
• ECOG Performance Status 0-3
• Must have completed any other oncologic therapies at least 15 days prior to planned start of study procedures (preferably 30 days) and must have no plans to initiate systemic therapy until after study follow up is complete -OR- must be recorded by physician to have an active candidate lesion that is unresponsive to ongoing systemic therapy.
• Females of childbearing potential should have negative urine or serum pregnancy test within 14 days prior to initiation of study scans.
• Demonstrate adequate organ function: determined by ANC, platelets, hemoglobin, with no gross hematuria
• For Cohort II only: Patient is dispositioned to undergo SBRT to a bone or lung tumor

You may not qualify if:

• Clinically significant blood glucose abnormalities that preclude a satisfactory FDG PET/CT scan.
• Previous history of external radiotherapy where prior radiotherapy fields are anticipated to overlap with the radiotherapy fields required for the present study
• Diffuse metastatic process (leptomeningeal disease, peritoneal carcinomatosis, diffuse bone marrow involvement, etc.)
• PET-avid structures not intended for radiation are within 2cm from target on third-party diagnostic PET/CT as assessed by investigator
• Known allergy to FDG
• Known psychiatric or substance abuse disorder that would interfere with conduct of the study
• Pregnant, breast-feeding or expecting to conceive during the study
• Patient weight exceeding the weight limit outlined per IFU.
• For Cohort II only: Patients with pacemakers and other implantable devices who are deemed to be at high risk by the treating physician for complications secondary to radiotherapy.
• For Cohort II only: Patients with bone lesions who are determined to be high risk by the treating physician for pathologic fracture prior to beginning radiotherapy.
• For Cohort II only: Active inflammatory bowel disease, scleroderma, or other disorder deemed to be a risk factor for excess toxicity in the area of treatment by the treating physician.

Sponsors & Collaborators

• RefleXion Medical: lead

Study Sites (2)

Stanford University

Stanford, California, 94305, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Neoplasms; Lung Neoplasms; Bone Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Bone Diseases; Musculoskeletal Diseases

Results Point of Contact

• Title: Debradenise Brooks
• Organization: RefleXion

dbrooks@reflexion.com

16504828435

Study Officials

• Daniel Chang, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Aurelie Garant, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, prospective study. The study is divided into two sequential cohorts of patients with one targetable primary or metastatic lesion in either the lungs or bone. Patients with multiple metastases can be accrued, but these investigations will focus on only one lesion per patient. Cohort I seeks to identify the Recommended RefleXion FDG dose (RRFD), which is the dose of administered FDG that allows for functioning of the RefleXion system. To that end, dose levels of 15 mCi and 20 mCi (if required) are assessed sequentially in an escalation protocol. The RRFD identified in Cohort I is utilized in Cohort II, to emulate and assess the dose delivery performance of the end-to-end BgRT workflow.

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 9, 2021
• Study Start: March 26, 2021
• Primary Completion: December 20, 2021
• Study Completion: December 20, 2021
• Last Updated: October 31, 2023
• Results First Posted: October 24, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)