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Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) in Recurrent Rectal Cancer (IMPARC)

Primary Purpose

Recurrent Rectal Cancer

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy
MEVION S250i Hyperscan and Adaptive Aperture Proton Therapy Machine
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Rectal Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • History of biopsy-proven adenocarcinoma of the rectum, anus or rectosigmoid junction of any stage now with recurrent disease in the pelvis
  • One prior course of radiation therapy to the pelvis for rectal cancer
  • ECOG performance status 0-2
  • At least 18 years of age
  • 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.
  • Able to understand and willing to sign an IRB-approved written informed consent document.

Exclusion Criteria:

  • Patients with pre-existing radiosensitizing conditions, such as connective tissue disorders (i.e. lupus, scleroderma) and genetic mutations (i.e. ataxia-telangiectasia)
  • A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease, basal cell or squamous cell carcinoma of the skin that were treated with local resection only, or carcinoma in situ of the cervix. Patients with history of prostate cancer treated without radiotherapy and no evidence of disease are eligible
  • More than one prior course of radiation to the pelvis for rectal cancer
  • Prior radiation to the pelvis for disease other than rectal cancer
  • Current treatment with any investigational agents.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or unstable angina pectoris
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of study entry.

Sites / Locations

  • Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose Level 1: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT)

Dose Level 2: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT)

Dose Level 3: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT)

Arm Description

Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 1. The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).

Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 2. The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).

Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 3. The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) of reirradiation using hypofractionated IMPT
MTD is defined as the dose associated with a 35% probability of dose-limiting toxicity (DLT). DLT is defined as any toxicity listed below that occurs within 6 months from start of treatment and is considered possibly, probably, or definitely related to proton reirradiation: Any grade 5 toxicities Any grade 4-5 GI toxicities Bowel obstruction Grade 3-5: diarrhea; anal, colonic, or bowel ulcers; bladder perforation; any fistula formations; peripheral motor/sensory neuropathy of the pelvis above baseline; osteonecrosis/soft tissue necrosis; radiation dermatitis; hematuria; hematochezia; bowel/pelvic hemorrhage; reproductive tract toxicity Toxicity will be graded using CTCAE v5

Secondary Outcome Measures

Clinical complete response rate
-DRE, endoscopy, and cross sectional imaging will be used to measure clinical complete response rate
Median freedom from locoregional progression (FFLP)
-Defined as time from end of radiation therapy to date of first instance of local or regional tumor progression
Median overall survival (OS)
Median progression-free survival (PFS)
-Defined as time from end of radiation therapy to the earliest date of locoregional progression, distant progression, or death from any cause
Change in quality of life as measured by the EORTC QLQ-C30
-The EORTC QLQ-C30 consists of a 30-question questionnaire, which assesses patient well-being with five functional scales (the physical, role, emotional, cognitive, social, and global). It also includes three symptom scales (fatigue, pain, nausea/vomiting) and six single items (dyspnea, sleep disturbance, appetite loss, diarrhea, constipation, and financial impact). Single-item QL scores for overall physical condition (question 29), overall quality of life (question 30), and the global and social functioning scales have been shown to be prognostic for overall survival in adult patients with advanced malignancies
Change in quality of life as measured by the EORTC QLQ-CR29
-The QLQ-CR29 contains 29 questions, including items in 4 scales (urinary frequency, blood/mucus in stools, stool frequency, body image) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest for men, sexual interest for women, impotence, dyspareunia). There are 11 items allocated for specific sub-populations, including males, females, and stoma patients. Scores of the QLQ-CR29 can be linearly transformed to provide a score from 0 to 100, with higher scores representing higher levels of functioning on the functional scales, greater degrees of symptomatology on the symptom scales and improved QOL on the global QOL scale
Frequency of acute adverse events as measured by CTCAE v 5.0
Frequency of late adverse events as measured by CTCAE v 5.0

Full Information

First Posted
March 29, 2021
Last Updated
August 21, 2023
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT04827732
Brief Title
Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) in Recurrent Rectal Cancer
Acronym
IMPARC
Official Title
Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) in the Reirradiation of Locoregionally Recurrent Rectal Cancer - IMPARC
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 4, 2021 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
May 31, 2025 (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 purpose of this trial is to determine the maximum tolerated dose (MTD) of hypofractionated IMPT for the reirradiation of locoregionally recurrent rectal cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Rectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 1: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT)
Arm Type
Experimental
Arm Description
Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 1. The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).
Arm Title
Dose Level 2: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT)
Arm Type
Experimental
Arm Description
Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 2. The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).
Arm Title
Dose Level 3: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT)
Arm Type
Experimental
Arm Description
Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 3. The use of Intensity Modulated Radiation Therapy (IMRT) with photon beam therapy is permitted at the discretion of the treating investigator in order to avoid extended treatment delays due to logistical reasons (e.g. machine downtime).
Intervention Type
Radiation
Intervention Name(s)
Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy
Other Intervention Name(s)
IMPT
Intervention Description
When feasible it is strongly recommended that radiotherapy begin on a Monday
Intervention Type
Device
Intervention Name(s)
MEVION S250i Hyperscan and Adaptive Aperture Proton Therapy Machine
Intervention Description
-The device that will administer the IMPT
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of reirradiation using hypofractionated IMPT
Description
MTD is defined as the dose associated with a 35% probability of dose-limiting toxicity (DLT). DLT is defined as any toxicity listed below that occurs within 6 months from start of treatment and is considered possibly, probably, or definitely related to proton reirradiation: Any grade 5 toxicities Any grade 4-5 GI toxicities Bowel obstruction Grade 3-5: diarrhea; anal, colonic, or bowel ulcers; bladder perforation; any fistula formations; peripheral motor/sensory neuropathy of the pelvis above baseline; osteonecrosis/soft tissue necrosis; radiation dermatitis; hematuria; hematochezia; bowel/pelvic hemorrhage; reproductive tract toxicity Toxicity will be graded using CTCAE v5
Time Frame
Through 6 months from start of treatment for all participants enrolled (estimated to be 42 months)
Secondary Outcome Measure Information:
Title
Clinical complete response rate
Description
-DRE, endoscopy, and cross sectional imaging will be used to measure clinical complete response rate
Time Frame
Within 6 weeks to 3 months post-completion of radiation therapy (estimated to be 7 weeks to 3 months and 1 week))
Title
Median freedom from locoregional progression (FFLP)
Description
-Defined as time from end of radiation therapy to date of first instance of local or regional tumor progression
Time Frame
At 12 months post-radiation therapy (estimated to be 12 months and 1 week)
Title
Median overall survival (OS)
Time Frame
At 12 months post-radiation therapy (estimated to be 12 months and 1 week)
Title
Median progression-free survival (PFS)
Description
-Defined as time from end of radiation therapy to the earliest date of locoregional progression, distant progression, or death from any cause
Time Frame
At 12 months post-radiation therapy (estimated to be 12 months and 1 week)
Title
Change in quality of life as measured by the EORTC QLQ-C30
Description
-The EORTC QLQ-C30 consists of a 30-question questionnaire, which assesses patient well-being with five functional scales (the physical, role, emotional, cognitive, social, and global). It also includes three symptom scales (fatigue, pain, nausea/vomiting) and six single items (dyspnea, sleep disturbance, appetite loss, diarrhea, constipation, and financial impact). Single-item QL scores for overall physical condition (question 29), overall quality of life (question 30), and the global and social functioning scales have been shown to be prognostic for overall survival in adult patients with advanced malignancies
Time Frame
Prior to start of radiation therapy, 1-2 weeks post radiation therapy, 3 months post radiation therapy, 6 months post radiation therapy, 9 months post radiation therapy and 12 months post radiation therapy
Title
Change in quality of life as measured by the EORTC QLQ-CR29
Description
-The QLQ-CR29 contains 29 questions, including items in 4 scales (urinary frequency, blood/mucus in stools, stool frequency, body image) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest for men, sexual interest for women, impotence, dyspareunia). There are 11 items allocated for specific sub-populations, including males, females, and stoma patients. Scores of the QLQ-CR29 can be linearly transformed to provide a score from 0 to 100, with higher scores representing higher levels of functioning on the functional scales, greater degrees of symptomatology on the symptom scales and improved QOL on the global QOL scale
Time Frame
Prior to start of radiation therapy, 1-2 weeks post radiation therapy, 3 months post radiation therapy, 6 months post radiation therapy, 9 months post radiation therapy and 12 months post radiation therapy
Title
Frequency of acute adverse events as measured by CTCAE v 5.0
Time Frame
From start of treatment through 3 months after completion of radiation therapy (estimated to be 3 months and 1 week)
Title
Frequency of late adverse events as measured by CTCAE v 5.0
Time Frame
From 3 month post-completion of radiation therapy to 12 months post-completion of radiation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: History of biopsy-proven adenocarcinoma of the rectum, anus or rectosigmoid junction of any stage now with recurrent disease in the pelvis One prior course of radiation therapy to the pelvis for rectal cancer ECOG performance status 0-2 At least 18 years of age 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. Able to understand and willing to sign an IRB-approved written informed consent document. Exclusion Criteria: Patients with pre-existing radiosensitizing conditions, such as connective tissue disorders (i.e. lupus, scleroderma) and genetic mutations (i.e. ataxia-telangiectasia) A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease, basal cell or squamous cell carcinoma of the skin that were treated with local resection only, or carcinoma in situ of the cervix. Patients with history of prostate cancer treated without radiotherapy and no evidence of disease are eligible More than one prior course of radiation to the pelvis for rectal cancer Prior radiation to the pelvis for disease other than rectal cancer Tumor in the rectum/colon requiring radiation therapy to the full circumference of the rectum/colon. Current treatment with any investigational agents. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or unstable angina pectoris Pregnant and/or breastfeeding. Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of study entry.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hyun Kim, M.D.
Phone
314-362-8567
Email
kim.hyun@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hyun Kim, M.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
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyun Kim, M.D.
Phone
314-362-8567
Email
kim.hyun@wustl.edu
First Name & Middle Initial & Last Name & Degree
Hyun Kim, M.D.
First Name & Middle Initial & Last Name & Degree
Re-I Chin, M.D.
First Name & Middle Initial & Last Name & Degree
Carl DeSelm, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Yi Huang, M.S.

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

Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) in Recurrent Rectal Cancer

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