Palliative Spatially Fractionated (GRID) Radiotherapy Using Intensity Modulated Proton Therapy

A Phase I Trial of Palliative Spatially Fractionated (GRID) Radiotherapy Using Intensity Modulated Proton Therapy

Spatially fractionated radiotherapy (SFRT or GRID) addresses some limitations of traditional stereotactic body radiation therapy by relying on beam collimation to create high-dose "peaks" and intervening low-dose "valleys" throughout the target volume. Standard palliative radiotherapy regimens provide limited durability of response, and there are challenges with delivery to large tumors or in previously irradiated fields. In this study, Proton GRID radiotherapy will be used to deliver three-fraction palliative radiotherapy to patients with tumors needing palliative radiation. The safety and efficacy of this approach will be assessed. It is hypothesized that GRID is highly effective, immunogenic, and associated with low rates of toxicity.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Cancer; Unresectable Solid Tumor
• Intervention / Treatment: Radiation: Proton GRID Radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anthony Apicelli, M.D.; Phone Number: 314-362-8610; Email: apicella@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Stephanie Perkins, M.D.
      • Sub-Investigator: Clifford Robinson, M.D.
      • Sub-Investigator: Tianyu Zhao, Ph.D.
      • Sub-Investigator: Nels Knutson, Ph.D.
      • Sub-Investigator: Michael Prusator, Ph.D.
      • Contact: Anthony Apicelli, M.D.; Phone Number: 314-362-8610; Email: apicella@wustl.edu
      • Principal Investigator: Anthony Apicelli, M.D.
      • Sub-Investigator: Jeff Szymanski, M.D., Ph.D.
      • Sub-Investigator: Justin Barnes, M.D.
      • Sub-Investigator: Yi Huang, M.S.
      • Sub-Investigator: Xiandong Zhao, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed cancer diagnosis.

• Planning to undergo palliative radiotherapy to unresectable or metastatic target lesion ≥ 4.5 cm in any dimension as measured with radiographic imaging or with calipers by clinical exam.

  • Cohort A: 10 patients with lesions that have been previously irradiated.
  • Cohort B: 10 patients with lesions that have not been previously irradiated.
• ECOG performance status ≤ 3
• At least 18 years of age.
• Radiotherapy is known to be teratogenic. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 6 months after completion of the study
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Patients with tumors in need of urgent surgical intervention, such as life-threatening bleeding or those at high risk for pathologic fracture and amenable to surgical intervention.
• Patients with a superficial target lesion ≤ 1 cm deep to skin surface who initially had a superficial lesion irradiated, if the target lesion was in the area of the prior irradiation.
• Currently receiving any cytotoxic cancer therapy regimens or VEGF inhibitors that will overlap with the proton GRID administration.
• Cytotoxic chemotherapy and VEGF inhibitors prior to radiotherapy or planned after radiotherapy delivery are allowed at the discretion of the treating radiation oncologist. This includes continuing a treatment plan which was initiated prior to the start of radiotherapy. A 2-week washout is recommended, but not required.
• Pregnant. Women of childbearing potential must have a negative pregnancy test within 20 days of study entry.
• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Reirradiation of Treatment Fields; Radiotherapy will consist of 20 Gy proton GRID radiotherapy x 3 fractions.	Radiation: Proton GRID Radiotherapy; The proton GRID radiotherapy prescription dose is 20 Gy x 3 fractions to the tumor, with an integrated dose of 6 Gy x 3 fractions to the PTV. Treatment to multiple lesions within the PTV is allowed (ex. a dominant lesion plus satellites). Multiple proton GRID radiotherapy plans may be delivered on the same day or different days, but they cannot overlap.
Experimental: Cohort B: De Novo Radiation Treatment Fields; Radiotherapy will consist of 20 Gy proton GRID radiotherapy x 3 fractions.	Radiation: Proton GRID Radiotherapy; The proton GRID radiotherapy prescription dose is 20 Gy x 3 fractions to the tumor, with an integrated dose of 6 Gy x 3 fractions to the PTV. Treatment to multiple lesions within the PTV is allowed (ex. a dominant lesion plus satellites). Multiple proton GRID radiotherapy plans may be delivered on the same day or different days, but they cannot overlap.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of treatment-related acute toxicity	-Grade per CTCAE v5.0.	From start of treatment through 90 days
Rate of treatment-related late toxicity	-Grade per CTCAE v5.0.	From day 91 through 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of target lesion local control		3 months
Change in PRO-CTCAE assessment	PRO-CTCAE is a standardized inventory to collected patient reported symptomatic adverse events in clinical trials.	Baseline, at last day of radiotherapy (day 3), within 2 weeks after completion of radiotherapy (day 14), 30 days, 90 days, 180 days, and 360 days
Change in PROMIS Global Health	PROMIS Global Health is a 10-item patient-reported questionnaire that assesses health related quality of life compared with normal values for the general population with the response options presented as a 5-point (as well as a single 11-point) rating scale. The question that uses an 11-point scale uses a response scale of 0-10 that is recoded to 5 categories (0 = 1; 1-3 = 2; 4-6 = 3; 7-9 = 4; 10 = 5). The results of the questions are used to calculate two summary scores: a Global Physical Health Score and a Global Mental Health score. These scores are then standardized to the general population, using the "T-Score". The average "T-Score" for the United States population is 50 points, with a standard deviation of 10 points. Higher scores are indicative of a healthier patient.	Baseline, at last day of radiotherapy (day 3), within 2 weeks after completion of radiotherapy (day 14), 30 days, 90 days, 180 days, and 360 days

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Anthony Apicelli, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: April 13, 2023
• First Submitted That Met QC Criteria: April 25, 2023
• First Posted (Actual): April 26, 2023

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: cancer; palliative radiotherapy; stereotactic body radiotherapy (SBRT); proton; spatially fractionated radiotherapy; GRID; stereotactic ablative radiotherapy (SABR)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: 202304011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Available data will include de-identified individual participant data collected during the trial.
• IPD Sharing Time Frame: Beginning 3 months after publication. No end date
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal may be granted data access. Proposals should be directed to apicellia@wustl.edu. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No