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

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

The purpose of this trial is to determine the maximum tolerated dose (MTD) of hypofractionated IMPT for the reirradiation of locoregionally recurrent rectal cancer.

Study Overview

• Status: Terminated
• Conditions: Recurrent Rectal Cancer
• Intervention / Treatment: Radiation: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy; Device: MEVION S250i Hyperscan and Adaptive Aperture Proton Therapy Machine

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT); Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 1 (30 Gy).; 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).	Radiation: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy; When feasible it is strongly recommended that radiotherapy begin on a Monday; Other Names: IMPT; Device: MEVION S250i Hyperscan and Adaptive Aperture Proton Therapy Machine; -The device that will administer the IMPT
Experimental: Dose Level 2: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT); Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 2 (35 Gy).; 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).	Radiation: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy; When feasible it is strongly recommended that radiotherapy begin on a Monday; Other Names: IMPT; Device: MEVION S250i Hyperscan and Adaptive Aperture Proton Therapy Machine; -The device that will administer the IMPT
Experimental: Dose Level 3: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT); Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level 3 (40 Gy).; 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).	Radiation: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy; When feasible it is strongly recommended that radiotherapy begin on a Monday; Other Names: IMPT; Device: MEVION S250i Hyperscan and Adaptive Aperture Proton Therapy Machine; -The device that will administer the IMPT
Experimental: Dose Level -1: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT); Radiotherapy will consist of five fractions, delivered once daily, with pencil beam scanning proton beam therapy using the defined dose in dose level -1 (25 Gy).; 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).	Radiation: Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy; When feasible it is strongly recommended that radiotherapy begin on a Monday; Other Names: IMPT; Device: MEVION S250i Hyperscan and Adaptive Aperture Proton Therapy Machine; -The device that will administer the IMPT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 toxicitiesAny grade 4-5 GI toxicitiesBowel obstructionGrade 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	From start of treatment through 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Complete Response Rate	-DRE, endoscopy, and cross-sectional imaging will be used to measure clinical complete response rate	Within 6 weeks to 3 months post-completion of radiation therapy (range 7-14 weeks)
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	Through completion of follow-up (full range 1.81 months-13.87 months)
Median Overall Survival (OS)	Defined as time from end of radiation therapy to date that at least 50% of patients died	Through completion of follow-up (full range 4.4 months to 13.87 months)
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	Through completion of follow-up (full range 1.81 months-13.87 months)
Median Change in Quality of Life (QoL) Score as Measured by The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)	30 question survey which assesses patient well-being with 5 functional scales, 9 symptom scales, & global health scale. Scores for each scale range from 0-100. Higher score for the functional scale & global health represent high functioning, while high score for symptom scale represents high symptomatology. Median scores were taken for each scale for each dose level and the different between pre-treatment and post-treatment scores were calculated to determine change in score over time. For functional scales and global health status, negative values represent improved functionality/quality of life, while positive values represent diminished functionality. For symptom scales, the opposite is true. If patients did not complete the the survey at each time point, their data was censored. Data values were averaged prior to 3 months. Differences were taken between baseline values and the average value calculated of post-RT up to 3 months.	Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment
Median Change in Quality of Life (QoL) Score as Measured by The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)	30 question survey which assesses patient well-being with 5 functional scales, 9 symptom scales, & global health scale. Scores for each scale range from 0-100. Higher score for the functional scale & global health represent high functioning, while high score for symptom scale represents high symptomatology. Median scores were taken for each scale for each dose level and the different between pre-treatment and post-treatment scores were calculated to determine change in score over time. For functional scales and global health status, negative values represent improved functionality/quality of life, while positive values represent diminished functionality. For symptom scales, the opposite is true. If patients did not complete the survey at each time point, their data was censored. Data values were averaged from 3-12 months. Differences were taken between baseline values and the average value calculated of post-RT from 3-12 months.	Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment
Median Change in Quality of Life (QoL) Score as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer Module 29 (EORTC QLQ-CR29)	29 question survey which assesses quality of life for patients with colorectal cancer including functional & symptom status. The survey includes 4 multi-item scales & 19 single-item scales. Scores are linearly transformed to provide a score from 0-100. A high score for functional scales represents high level of functioning, while a high score for symptom scale represents high level of symptoms. Median scores were taken for each scale & the difference between baseline & varying time points was reported. Negative value represents improved function for a functional scale item, & worsening symptoms for symptom scale items. Positive values represent the converse. If patients did not complete the survey at each time point, their data was censored. Data values were averaged prior to 3 months. Differences were taken between pre-treatment (baseline) values and the average value calculated of post-RT up to 3 months.	Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment
Median Change in Quality of Life (QoL) Score as Measured by the by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer Module 29 (EORTC QLQ-CR29)	29 question survey which assesses quality of life for patients with colorectal cancer including functional & symptom status. The survey includes 4 multi-item scales & 19 single-item scales. Scores are linearly transformed to provide a score from 0-100. A high score for functional scales represents high level of functioning, while a high score for symptom scale represents high level of symptoms. Median scores were taken for each scale & the difference between baseline & varying time points was reported. Negative value represents improved function for a functional scale item, & worsening symptoms for symptom scale items. Positive values represent the converse. If patients did not complete the survey at each time point, their data was censored. Data values were averaged from 3-12 months. Differences were taken between baseline values and the average value calculated of post-RT from 3-12 months	Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment
Frequency of Treatment-related Acute Adverse Events as Measured by CTCAE v 5.0		From start of treatment through 3 months after completion of radiation therapy (estimated to be 3 months and 1 week)
Frequency of Treatment-related Late Adverse Events as Measured by CTCAE v 5.0		From 3 month post-completion of radiation therapy to 12 months post-completion of radiation therapy

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Michael Waters, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2021
• Primary Completion (Actual): July 29, 2024
• Study Completion (Actual): November 18, 2024

Study Registration Dates

• First Submitted: March 29, 2021
• First Submitted That Met QC Criteria: March 29, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: 202103218

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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