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Proton Beam Therapy in the Treatment of Esophageal Cancer

Primary Purpose

Esophagus Cancer, Esophageal Cancer, Cancer of the Esophagus

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Proton beam therapy
Patient-Reported Outcome Measures
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophagus Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.
  • English speaker.
  • Financial coverage for proton therapy.

Exclusion Criteria:

  • 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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1: Resectable (proton beam therapy)

Arm 2: Unresectable (proton beam therapy)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change from baseline to 6 months following end of chemoradiation in patient-reported outcomes of PBT for esophageal cancer as measured by the 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, ranking their symptoms on a 0 (no problems) to 10 (worst imaginable) scale before treatment, weekly during treatment, and in treatment follow-up.
Patient-reported outcomes of PBT for esophageal cancer as measured by the EQ-5D
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.
Patient-reported outcomes of PBT for esophageal cancer as measured by the SF-12
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.
Patient-reported outcomes of PBT for esophageal cancer as measured by the MOS Social Support
The 19-item Medical Outcomes Study (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 with higher scores indicating a greater availability of social support.
Patient-reported outcomes of PBT for esophageal cancer as measured by the 4-Item CES-D
The Center for Epidemiological Studies Depression Scale (CES-D) 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.
Patient-reported outcomes of PBT for esophageal cancer as measured by the 4-Item CES-D
The Center for Epidemiological Studies Depression Scale (CES-D) 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.
Patient-reported outcomes of PBT for esophageal cancer as measured by the MOS Social
The 19-item Medical Outcomes Study (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 with higher scores indicating a greater availability of social support.
Patient-reported outcomes of PBT for esophageal cancer as measured by the SF-12
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.
Patient-reported outcomes of PBT for esophageal cancer as measured by the EQ-5D
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.
Change in baseline to 12 months following end of chemoradiation in patient-reported outcomes of PBT for esophageal cancer as measured by the 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, ranking their symptoms on a 0 (no problems) to 10 (worst imaginable) scale before treatment, weekly during treatment, and in treatment follow-up.
Physician-reported toxicity of PBT for esophageal cancer
-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

Secondary Outcome Measures

Progression-free survival (PFS) of proton beam therapy (PBT) for patients with resectable versus unresectable esophageal cancer
-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Overall survival (OS)of PBT for patients with resectable versus unresectable esophageal cancer
Progression-free survival (PFS) of proton beam therapy (PBT) for patients with resectable
-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Overall survival (OS)of PBT for patients with resectable versus unresectable esophageal

Full Information

First Posted
March 15, 2018
Last Updated
May 25, 2023
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT03482791
Brief Title
Proton Beam Therapy in the Treatment of Esophageal Cancer
Official Title
A Phase II Study of Proton Beam Therapy in the Treatment of Esophageal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 19, 2018 (Actual)
Primary Completion Date
September 13, 2022 (Actual)
Study Completion Date
August 9, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophagus Cancer, Esophageal Cancer, Cancer of the Esophagus

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Resectable (proton beam therapy)
Arm Type
Experimental
Arm Description
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
Arm Title
Arm 2: Unresectable (proton beam therapy)
Arm Type
Experimental
Arm Description
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
Intervention Type
Radiation
Intervention Name(s)
Proton beam therapy
Other Intervention Name(s)
PBT
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Patient-Reported Outcome Measures
Other Intervention Name(s)
PROs
Intervention Description
-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
Primary Outcome Measure Information:
Title
Change from baseline to 6 months following end of chemoradiation in patient-reported outcomes of PBT for esophageal cancer as measured by the MDASI-Plus
Description
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, ranking their symptoms on a 0 (no problems) to 10 (worst imaginable) scale before treatment, weekly during treatment, and in treatment follow-up.
Time Frame
6 months following chemoradiation (estimated to be 9 months)
Title
Patient-reported outcomes of PBT for esophageal cancer as measured by the EQ-5D
Description
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.
Time Frame
6 months following chemoradiation (estimated to be 9 months)
Title
Patient-reported outcomes of PBT for esophageal cancer as measured by the SF-12
Description
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.
Time Frame
6 months following chemoradiation (estimated to be 9 months)
Title
Patient-reported outcomes of PBT for esophageal cancer as measured by the MOS Social Support
Description
The 19-item Medical Outcomes Study (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 with higher scores indicating a greater availability of social support.
Time Frame
6 months following chemoradiation (estimated to be 9 months)
Title
Patient-reported outcomes of PBT for esophageal cancer as measured by the 4-Item CES-D
Description
The Center for Epidemiological Studies Depression Scale (CES-D) 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.
Time Frame
6 months following chemoradiation (estimated to be 9 months)
Title
Patient-reported outcomes of PBT for esophageal cancer as measured by the 4-Item CES-D
Description
The Center for Epidemiological Studies Depression Scale (CES-D) 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.
Time Frame
12 months following chemoradiation (estimated to be 15 months)
Title
Patient-reported outcomes of PBT for esophageal cancer as measured by the MOS Social
Description
The 19-item Medical Outcomes Study (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 with higher scores indicating a greater availability of social support.
Time Frame
12 months following chemoradiation (estimated to be 15 months)
Title
Patient-reported outcomes of PBT for esophageal cancer as measured by the SF-12
Description
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.
Time Frame
12 months following chemoradiation (estimated to be 15 months)
Title
Patient-reported outcomes of PBT for esophageal cancer as measured by the EQ-5D
Description
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.
Time Frame
12 months following chemoradiation (estimated to be 15 months)
Title
Change in baseline to 12 months following end of chemoradiation in patient-reported outcomes of PBT for esophageal cancer as measured by the MDASI-Plus
Description
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, ranking their symptoms on a 0 (no problems) to 10 (worst imaginable) scale before treatment, weekly during treatment, and in treatment follow-up.
Time Frame
12 months following chemoradiation (estimated to be 15 months)
Title
Physician-reported toxicity of PBT for esophageal cancer
Description
-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
Time Frame
6 months following chemoradiation (estimated to be 9 months)
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS) of proton beam therapy (PBT) for patients with resectable versus unresectable esophageal cancer
Description
-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time Frame
2 years following chemoradiation (estimated to be 2 years and 3 months)
Title
Overall survival (OS)of PBT for patients with resectable versus unresectable esophageal cancer
Time Frame
2 years following chemoradiation (estimated to be 2 years and 3 months)
Title
Progression-free survival (PFS) of proton beam therapy (PBT) for patients with resectable
Description
-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time Frame
5 years following chemoradiation (estimated to be 5 years and 3 months)
Title
Overall survival (OS)of PBT for patients with resectable versus unresectable esophageal
Time Frame
5 years following chemoradiation (estimated to be 5 years and 3 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. English speaker. Financial coverage for proton therapy. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Vlacich, M.D., Ph.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

Proton Beam Therapy in the Treatment of Esophageal Cancer

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