Pivotal Study of Proton Radiotherapy Treatments Using Fixed Beam Chair-Based Delivery System

Study Overview
=================
Brief Summary
-----------------
This study with Chair-Based, Gantry-less Proton System (CBGS) (aka P-CURE Proton Beam Therapy System or Fixed Beam Chair-based Delivery System) is composed of 3 arms, as following: ARM1: Patients with locally recurrent, previously irradiated thoracic cancer indicated for re- irradiation. ARM2: Patients with recurrent Head and Neck, Brain and Spinal Cord tumors, indicated for re- irradiation. ARM3: Patients with unresectable pancreatic cancer. The primary objectives of the study for all arms are: 1. to describe the efficacy (local control after 3 month) and acute toxicity for patients treated with a fully-integrated CBGS and (2) to compare treatment plans between the fully-integrated CBGS and Photon therapy defined for each patient, based upon OAR sparing for comparable target coverage.

Official Title
-----------------
Pivotal Study of Proton Radiotherapy Treatments Using Fixed Beam Chair-Based Delivery System

Conditions
-----------------
Thoracic Cancer, Pancreatic Cancer Non-resectable, Brain Cancer, Head Cancer, Neck Cancer

Intervention / Treatment
-----------------
* Device: Proton Radiation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathologically (histologically or cytologically) proven malignancy Treatment planning analysis shows advantage to proton over photon treatments both malignancies (such as thoracic tumors) as well as metastatic lesions (such as metastatic breast cancer or colorectal cancer to the lungs) are allowed Patient must have CT confirmation of the tumor Patients must have a life expectancy of > 6 months Patients must have measurable disease to be treated with proton radiation (minimum tumor dimension at least 10 mm on CT imaging). Patients must be a candidate for definitive radiation dose There are no limits on prior therapy. Patients are allowed to have prior chemotherapy and surgery. Patients are allowed to have concurrent chemotherapy with radiation treatment. Patients are allowed to have chemotherapy or surgery after radiation treatment Exclusion Criteria: Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months Transmural myocardial infarction within the last 6 months Chronic obstructive pulmonary disease exacerbation or other respiratory illness other than the diagnosed lung cancer requiring hospitalization or precluding study therapy within 30 days before registration Acquired immune deficiency syndrome (AIDS) based upon current CDC definition (protocol may be significantly immunosuppressive endangering AIDS patients) Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception Patients with life expectancy < 6 months Patients that participate in another, active clinical trial carried out concurrently with this protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with locally recurrent, previously irradiated thoracic cancer<br>Prospective study shall evaluate treatment efficacy, toxicity, QOL and plan parity in patients with recurrent thoracic cancer previously irradiated, undergoing proton radiation therapy | Device: Proton Radiation<br>* Proton beam radiotherapy, first proposed by Robert Wilson at Harvard University in 1946, utilizes an energetic beam of ionized hydrogen nuclei (protons) directed at the tumor volume to effect DNA damage of the targeted cells. Today, there are hundreds of proton treatment centers worldwide and it is considered standard treatment for certain malignancies and/or clinical scenarios<br>* Other names: Quality-of-Life Assessment;|
| Experimental: Patients with recurrent Head and Neck, Brain and Spinal Cord tumors, indicated for re- irradiation<br>The prospective study shall evaluate treatment Efficacy, Toxicity, Quality of Life (QOL), and plan parity in adult patients with recurrent Head and Neck and Brain cancer undergoing proton radiation therapy | Device: Proton Radiation<br>* Proton beam radiotherapy, first proposed by Robert Wilson at Harvard University in 1946, utilizes an energetic beam of ionized hydrogen nuclei (protons) directed at the tumor volume to effect DNA damage of the targeted cells. Today, there are hundreds of proton treatment centers worldwide and it is considered standard treatment for certain malignancies and/or clinical scenarios<br>* Other names: Quality-of-Life Assessment;|
| Experimental: Patients with unresectable pancreatic cancer<br>This prospective study shall evaluate treatment feasibility utilizing the CBGS for unresectable pancreatic cancer with concurrent chemotherapy | Device: Proton Radiation<br>* Proton beam radiotherapy, first proposed by Robert Wilson at Harvard University in 1946, utilizes an energetic beam of ionized hydrogen nuclei (protons) directed at the tumor volume to effect DNA damage of the targeted cells. Today, there are hundreds of proton treatment centers worldwide and it is considered standard treatment for certain malignancies and/or clinical scenarios<br>* Other names: Quality-of-Life Assessment;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Control | The duration of local control will be measured from the start date of protocol radiation until the date of progressive disease. Local control will be determined based on RECIST Criteria Version 1.1. | 3 months | 
| Acute Toxicity | Incidence of treatment-related grade 3-5 adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | 3 months | 
| Treatment Plan Comparison between Chair Based Proton System and Photon therapy | Analysis and comparison of dose volume histograms (DVHs) and isodoses for each modality | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | The time from study registration until the first occurrence of local, regional, or distant progression, or death from any cause, or until last follow-up | 2 years | 
| Overall Survival | The time from study registration until death or last follow-up | 2 years | 
| Long-term Toxicity | Incidence of treatment-related grade 3-5 adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | 2 Years | 
| Quality of Life | Lung Cancer Patients: FACT-Lung and EQ-5D Head and Neck Patients: EORTC QLQ-C30 and the EORTC QLQ-H&N35 Pancreas Patients: Quality of Life assessment using Patient Reported Outcomes | 2 years |