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

Sponsor

Washington University School of Medicine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05831579

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Unresectable Solid Tumor Metastatic Cancer	Radiation: Proton GRID Radiotherapy	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 30, 2023

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

Rate of treatment-related acute toxicity [From start of treatment through 90 days]
-Grade per CTCAE v5.0.
Rate of treatment-related late toxicity [From day 91 through 12 months]
-Grade per CTCAE v5.0.

Secondary Outcome Measures

Change in PRO-CTCAE assessment [Baseline, 14 days, 30 days, 3 months, 6 months, and 12 months]
PRO-CTCAE is a standardized inventory to collected patient reported symptomatic adverse events in clinical trials.
Change in PROMIS Global Health [Baseline, 14 days, 30 days, 3 months, 6 months, and 12 months]
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.
Rate of target lesion local control [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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.