Proton Pencil Beam Scanning GRID for Treatment of Bulky Tumors

Study Overview
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Brief Summary
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This is a single arm, phase I study, evaluating the feasibility, toxicity, and degree of tumor response after novel proton pencil beam scanning (PBS GRID) treatment in patients with bulky tumors that are difficult to manage.

Detailed Description
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The proton group at Sibley Memorial Hospital has developed a new method for multi-beam proton delivery making it possible to arrange and optimize GRID dosimetry and normal tissue sparing compared to other similar techniques. In this phase I pilot study, patients with bulky tumors will receive this novel method of GRID-therapy also called spatially-fractionated radiotherapy which involves delivering high dose radiation to small amounts of tumor in a manner that creates alternating regions of high and low dose radiation within the tumor and is often aligned in a grid pattern. In so doing, this study will ascertain the feasibility, safety and tumor response i.e. shrinkage and resectability of this treatment. Ultimately, the goal is to improve local outcomes of patients with bulky tumors and to offer new treatment options for patients with difficult-to-manage bulky tumors.

Official Title
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A Phase 1 Study of Proton Pencil Beam Scanning GRID for Treatment of Bulky Tumors (ProGRID)

Conditions
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Sarcoma, Melanoma

Intervention / Treatment
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* Radiation: Pro-GRID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 Histologically or cytologically confirmed invasive cancer Bulky tumor > 7 cm, determined clinically and/or radiographically, at the time of evaluation prior to enrollment Treated indicated for palliative intent Eastern Cooperative Oncology Group (ECOG) performance status < 2 Anticipated treatment deemed safe on pre-review by PI For patients with prior Radiation Therapy (RT): Dicoms must be available for dose fusion if overlap anticipated with GRID Willing and able to provide informed consent Discussion with medical oncology or surgical specialty Exclusion Criteria: Age < 18 ECOG performance status 3-4 Planned for definitive, curative management For patients with prior RT that overlaps with Pro-GRID: Dicoms not available Pregnant women Tumor encasing critical structure, as defined by the treating MD.

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: This is a single arm phase I study design, evaluating the feasibility (primary endpoint), toxicity (secondary endpoint), and degree of response (exploratory endpoint) after proton GRID therapy in patients with bulky tumors.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pro-GRID treatment Arm<br>Patients enrolled in this study will receive spatially-fractionated radiotherapy or GRID-therapy, which involves delivering a one-time treatment of high dose radiation to small amounts of tumor in a manner that creates alternating regions of high and low dose radiation within the tumor. Patients will receive 2 (lowest dose) to 18 Gy (highest dose) in a single fraction. | Radiation: Pro-GRID<br>* Study participants will receive a single treatment of Pro-GRID therapy. After which, the participants would be able to resume standard therapy (after one week) and receive additional radiotherapy one month after Pro-GRID therapy, if recommended. Participants will be in the study for one year. Follow-up appointments will be scheduled at 1, 3, 6 and 12 months posttreatment, and may include a history and physical exam, labs and/or a CT scan and toxicity assessments.<br>* Other names: Multi-beam proton Pencil Beam Scanning (PBS), termed Pro-GRID;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of the Pro-GRID intervention as assessed by success of intervention delivery for a number of participants | To assess the feasibility of successfully creating treatment plans and delivering a novel proton therapy called Pro-GRID. Feasibility will be determined by a successful intervention delivery for 10 of 12 patients with bulky solid tumors. | 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4) | To determine the rate of mild acute toxicity, defined as any CTCAE grade 2 or lower toxicity, and severe acute toxicity, defined as any CTCAE grade 3 or higher toxicity. | 3 months post-treatment | 
| Change in rate of treatment response of bulky tumors treated and not treated with proton GRID therapy | To determine the change in response rate for bulky tumors treated and not treated with Proton GRID by Response Evaluation Criteria in Solid Tumours (RECIST) criteria. | 1, 6 and 12 months post-treatment | 
| Change in degree of treatment response of bulky tumors treated and not treated with proton GRID therapy | Change in degree of treatment response would be measured by RECIST criteria (partial response, complete response, stable disease, or progression of disease). | 1, 6 and 12 months post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spatially-fractionated radiotherapy, GRID-therapy, Proton therapy, Sarcoma, Melanoma, Treatment resistant tumors