Proton Beam Therapy in the Treatment of Esophageal Cancer

NCT03482791 | Active Not Recruiting Results DMC FDA Device

• 1 other identifier: 201803092
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators plan to include both operable and inoperable patients with esophagus cancer in this prospective trial. Since both proton and photon treatments are biologically equivalent, the investigators do not expect a difference in tumor control compared to intensity modulated radiation therapy (IMRT). The investigators have a prospective experience of physician-reported toxicity and patient outcome using IMRT for patients with inoperable esophagus cancer that will serve as a comparison group. For the resectable patients receiving trimodality therapy (chemoradiation followed by surgery), the investigators will carefully track toxicity and patient outcomes prospectively. The central hypothesis is that the biologic efficacy for tumor control should be similar between protons and photons, and therefore survival measures should be similar between the two groups, but that the main difference lies in the total severe toxicities experienced by the patients undergoing therapy.

Conditions

Cancer of the Esophagus; Esophagus Cancer; Esophageal Cancer

Outcome Measures

Primary Outcomes (21)

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the MD Anderson Symptom Inventory (MDASI)-Plus

  The MDASI-Plus is a reliable, validated tool for assessing cancer-related symptoms regardless of therapy or specific cancer diagnosis. Patients are asked to fill out a twenty-seven question inventory. 21 questions ask the patient about the severity of their symptoms with answers ranging from 0=not present to 10=as bad as you can imagine. 6 questions ask the patient about how their symptoms interfered with their life with answers ranging from 0=did not interfere to 10=interfered completely. The higher the score the more severe symptom experience the patient experienced.

  Baseline, post completion of chemoradiation, 2 months, 4 months, and 6 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the EuroQol (EQ-5D) Questionnaire

  The EQ-5D is a standardized 2-part, patient-administered instrument used for direct and indirect assessment of health state utilities. The first part asks respondents to "check the ONE box \[next to the appropriate statement\] that best describes your health TODAY" for each of 5 health dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state. Both the 5-item index score and the VAS score are transformed into a utility score between 0 "Worst health state" and 1 "Best health state. The higher the score the better health a patient experienced.

  Baseline, post completion of chemoradiation, 2 months, 4 months, and 6 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the Medical Outcomes Study (MOS) Social Support Survey

  The 19-item MOS Social Support Survey was designed for use with patients with chronic diseases and measures how often different kinds of support are available, if needed. Response choices range from "none of the time" (1) to "all of the time" (5). A mean social support score for all 19 items is computed to a 0-100 scale with higher scores indicating a greater availability of social support.

  Baseline, post completion of chemoradiation, 2 months, 4 months, and 6 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the 4-Item Center for Epidemiological Studies Depression Scale (CES-D)

  The CES-D questionnaire is a 20-item measure which evaluates depressive symptoms. This trial will make use of the validated 4-item screening version in order to reduce participant burden. Possible range of scores is 0-60, with the higher scores indicating the presence of more symptomatology.

  Baseline, post completion of chemoradiation, 2 months, 4 months, and 6 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the MD Anderson Symptom Inventory (MDASI)-Plus

  The MDASI-Plus is a reliable, validated tool for assessing cancer-related symptoms regardless of therapy or specific cancer diagnosis. Patients are asked to fill out a twenty-seven question inventory. 21 questions ask the patient about the severity of their symptoms with answers ranging from 0=not present to 10=as bad as you can imagine. 6 questions ask the patient about how their symptoms interfered with their life with answers ranging from 0=did not interfere to 10=interfered completely. The higher the score the more severe symptom experience the patient experienced.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the EuroQol (EQ-5D) Questionnaire

  The EQ-5D is a standardized 2-part, patient-administered instrument used for direct and indirect assessment of health state utilities. The first part asks respondents to "check the ONE box \[next to the appropriate statement\] that best describes your health TODAY" for each of 5 health dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state. Both the 5-item index score and the VAS score are transformed into a utility score between 0 "Worst health state" and 1 "Best health state. The higher the score the better health a patient experienced.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the Medical Outcomes Study (MOS) Social Support Survey

  The 19-item MOS Social Support Survey was designed for use with patients with chronic diseases and measures how often different kinds of support are available, if needed. Response choices range from "none of the time" (1) to "all of the time" (5). A mean social support score for all 19 items is computed to a 0-100 scale with higher scores indicating a greater availability of social support.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the 4-Item Center for Epidemiological Studies Depression Scale (CES-D)

  The CES-D questionnaire is a 20-item measure which evaluates depressive symptoms. This trial will make use of the validated 4-item screening version in order to reduce participant burden. Possible range of scores is 0-60, with the higher scores indicating the presence of more symptomatology.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Physician-reported Toxicity of PBT for Esophageal Cancer

  Number of participants with grade 3 or higher specific cardiac, metabolism/nutrition, gastrointestinal, respiratory/thoracic/mediastinal, and skin/subcutaneous toxicity using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 related to PBT

  Through 6 months following chemoradiation (estimated to be 9 months)

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Mental Component Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher scores indicate better quality of life. MCS scores from the SF-12 are recoded, weighted, and summed, and standardized by the SF-12 scoring procedure. SF-12 is a licensed product and this procedure is implemented in the QualityMetric PRO CoRE software package. MCS range is 40-65.

  Baseline, post completion of chemoradiation, 2 months, 4 months, and 6 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Physical Component Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher scores indicate better quality of life. PCS scores from the SF-12 are recoded, weighted, and summed, and standardized by the SF-12 scoring procedure. SF-12 is a licensed product and this procedure is implemented in the QualityMetric PRO CoRE software package. PCS range is 30-55.

  Baseline, post completion of chemoradiation, 2 months, 4 months, and 6 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Physical Component Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher scores indicate better quality of life. PCS scores from the SF-12 are recoded, weighted, and summed, and standardized by the SF-12 scoring procedure. SF-12 is a licensed product and this procedure is implemented in the QualityMetric PRO CoRE software package. PCS range is 30-55.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Mental Component Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher scores indicate better quality of life. MCS scores from the SF-12 are recoded, weighted, and summed, and standardized by the SF-12 scoring procedure. SF-12 is a licensed product and this procedure is implemented in the QualityMetric PRO CoRE software package. MCS range is 40-65.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - General Health Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Lower mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-5.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Physical Function Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-3.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Physical Role Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-2.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Emotional Role Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-2.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Bodily Pain Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Lower mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-5.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Mental Health Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Lower mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-6.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Vitality Health Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Lower mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-6.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

• Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Social Functioning Score

  The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-5.

  Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months

Secondary Outcomes (2)

• Progression-free Survival (PFS) of Proton Beam Therapy (PBT) for Patients With Resectable

  5 years following chemoradiation (estimated to be 5 years and 3 months)

• Overall Survival (OS)of PBT for Patients With Resectable Versus Unresectable Esophageal

  5 years following chemoradiation (estimated to be 5 years and 3 months)

Study Arms (2)

Arm 1: Resectable (proton beam therapy)

EXPERIMENTAL

* Proton beam therapy: total dose of 50 or 50.4 Gy * Standard of care chemotherapy - the clinical trial doesn't dictate anything about the chemotherapy given, it is the treating physician's decision * Surgery should ideally be performed no later than 8 to 10 weeks after completing chemoradiation * Patient-reported outcome measures (PROs) performed at several time points

Radiation: Proton beam therapy; Other: Patient-Reported Outcome Measures

Arm 2: Unresectable (proton beam therapy)

EXPERIMENTAL

* Proton beam therapy: total dose of 59.4 or 60 Gy * Standard of care chemotherapy - the clinical trial doesn't dictate anything about the chemotherapy given, it is the treating physician's decision * Patient-reported outcome measures (PROs) performed at several time points

Radiation: Proton beam therapy; Other: Patient-Reported Outcome Measures

Interventions

Proton beam therapy RADIATION

* The daily prescription dose will be 1.8 or 2 Gy RBE ("Relative Biologic Equivalence") to be delivered to the periphery of the planning target volume (PTV). * The Mevion S-250 Proton Radiation Beam Therapy System will be used.

Also known as: PBT

Arm 1: Resectable (proton beam therapy); Arm 2: Unresectable (proton beam therapy)

Patient-Reported Outcome Measures OTHER

-Prior to start of therapy, end of chemoradiation (day of end of treatment or up to 1 week after), 8 weeks, 4, 6, 9, and 12-months following end of chemoradiation

Also known as: PROs

Arm 1: Resectable (proton beam therapy); Arm 2: Unresectable (proton beam therapy)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically documented adenocarcinoma or squamous cell carcinoma of the cervical or thoracic esophagus or gastroesophageal junction or cardia of stomach.
• Staged by PET/CT and esophagogastroduodenoscopy (EGD) or endoscopic ultrasound (EUS) OR CT w/contrast and EGD to have stage II or III disease per AJCC 7th edition guidelines
• Prior endoscopic mucosal resection (EMR) with a diagnosis of stage II or III esophageal cancer (AJCC 7th edition) is eligible, irrespective of margin status.
• Induction chemotherapy prior to concurrent chemoradiation is allowed.
• Prior thoracic radiation is allowable if degree of overlap with the esophageal radiotherapy treatment is deemed to be safe by the treating radiation oncologist.
• At least 18 years of age.
• ECOG performance status \< 2
• Normal bone marrow and organ function as defined below:
• WBC \> 2,500/mcL
• Platelets \> 75,000/mcl
• Total bilirubin \< 1.5 x institutional upper limit of normal (IULN)
• AST(SGOT)/ALT(SGPT) \< 3.0 x IULN
• Creatinine \< 1.5 x IULN OR Creatinine clearance \> 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• 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.
• Ability to understand and willingness to sign an IRB approved written informed consent document.

You may not qualify if:

• Planned treatment with radiation therapy alone without concurrent chemotherapy or chemotherapy alone.
• Previous or concomitant cancers within the past 3 years other than curatively treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, curative treatment for transitional cell carcinoma of the bladder, and low risk prostate cancer. Except for prostate cancer (which can be observed if low risk), other cancers listed must have been treated in the past 3 years without evidence of recurrence at the time of registration.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia not controlled by pacer device, myocardial infarction within 3 months of registration, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 7 days of the start of treatment.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Proton Therapy; Patient Reported Outcome Measures

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics; Health Care Surveys; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Services Research; Health Planning; Health Care Economics and Organizations; Patient Outcome Assessment; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Health Care Evaluation Mechanisms; Public Health; Environment and Public Health

Results Point of Contact

• Title: Gregory Vlacich, M.D., Ph.D.
• Organization: Washington University School of Medicine

gvlacich@wustl.edu

314-362-8610

Study Officials

• Gregory Vlacich, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: March 29, 2018
• Study Start: April 19, 2018
• Primary Completion: September 13, 2022
• Study Completion (Estimated): August 9, 2026
• Last Updated: April 2, 2026
• Results First Posted: April 6, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)