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

Not Applicable

Terminated

Conditions: Recurrent Rectal Cancer

Registration Number: NCT04827732

Lead Sponsor: Washington University School of Medicine

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 15

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 & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of Reirradiation Using Hypofractionated IMPT	From start of treatment through 6 months	* 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

Name	Time	Method
Median Overall Survival (OS)	Through completion of follow-up (full range 4.4 months to 13.87 months)	Defined as time from end of radiation therapy to date that at least 50% of patients died
Median Progression-free Survival (PFS)	Through completion of follow-up (full range 1.81 months-13.87 months)	-Defined as time from end of radiation therapy to the earliest date of locoregional progression, distant progression, or death from any cause
Clinical Complete Response Rate	Within 6 weeks to 3 months post-completion of radiation therapy (range 7-14 weeks)	-DRE, endoscopy, and cross-sectional imaging will be used to measure clinical complete response rate
Median Freedom From Locoregional Progression (FFLP)	Through completion of follow-up (full range 1.81 months-13.87 months)	-Defined as time from end of radiation therapy to date of first instance of local or regional tumor progression
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)	Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment	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.
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)	Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment	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.
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)	Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment	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
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

Trial Locations

Locations (1): Washington University School of Medicine
🇺🇸
St Louis, Missouri, United States
Washington University School of Medicine
🇺🇸St Louis, Missouri, United States