Study of High-Dose-Rate Endorectal Brachytherapy (HDRBT) in the Treatment of Locally Advanced Low Rectal Cancer

Study Overview
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Brief Summary
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This research is being done to see how effective high-dose rate endorectal brachytherapy (HDRBT) is in treating cancer of the lowest part of the bowel (rectum). In this study we want to try to decrease side effects and shorten the course of radiation treatment for patients with cancer of their rectum by using a high-dose rate endorectal brachytherapy (HDRBT). This is a different form of radiation than what is normally given (CRT). With HDRBT, the radiation is given through an applicator placed into the bowel next to the tumor. The radiation is directed at the tumor and a small area around it.

Detailed Description
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This study is a pilot study open to patients with clinical stage T2N1 or T3N0-1 resectable rectal cancer. The investigational tool being evaluated is high-dose endorectal brachytherapy (HDRBT) which is an FDA approved method to administer endoluminal radiation for low rectal cancer. This study assumes that the rate of pathological response to HDRBT will be similar to historical controls (conventional neoadjuvant chemoradiation). All patients will receive postoperative standard 5-fluorouracil (FU) based chemotherapy (at the discretion of the medical oncologist). The clinical response will be assessed with endoscopic/ultrasound, pelvic MRI and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. In addition, tissue and serum will be collected to evaluate for biological predictors of response to therapy. The endpoints of this study include adverse events (gastrointestinal toxicity), quality of life as measured by the quality of life questionnaire (QLQ)-C30, and tumor regression/response.

Official Title
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Phase II Study of High-Dose-Rate Endorectal Brachytherapy (HDRBT) in the Treatment of Locally Advanced Low Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Radiation: High-dose endorectal brachytherapy (HDRBT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed adenocarcinoma of the rectum Able to undergo local staging of the rectal tumor performed by MRI and/or endoscopic ultrasonography (EUS) demonstrating a T2N1 or T3N0-1 tumor Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Participants are willing to undergo initial therapy and if needed subsequent therapy prior to resection at Johns Hopkins Medical Institutions English as a primary language in order to complete the quality of life questionnaires Exclusion Criteria: Patients with tumors >12 cm from the anal verge. Near obstructing or bulky tumors which will not allow application of the endorectal probe Patients with distant metastatic disease Any pelvic lymph nodes outside of the mesorectum (iliac or inguinal) Prior history of radiation therapy to the pelvis Prior history of chemotherapy for rectal cancer Active connective tissue disease such as scleroderma or Crohn's disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: High-Dose-Rate Endorectal Brachytherapy (HDRBT)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HDRBT (High Dose Rectal Brachytherapy)<br>Radiation: High-dose endorectal brachytherapy The investigational tool being evaluated is high-dose endorectal brachytherapy (HDRBT) which is an FDA approved method to administer endoluminal radiation for low rectal cancer. A daily dose of 6.5 Gy over four consecutive days | Radiation: High-dose endorectal brachytherapy (HDRBT)<br>* The investigational tool being evaluated is high-dose endorectal brachytherapy (HDRBT) which is an FDA approved method to administer endoluminal radiation for low rectal cancer.<br>* Other names: HDRBT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Pathologic Complete Response | Those participants whose surgical pathology indicated that they had a complete response. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response of High-Dose-Rate Endorectal Brachytherapy (HDRBT) | Radiographic measurements of pelvic MRI and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging will be used to classify patients as responders or non-responders to HDRBT using standard RECIST criteria. Using RECIST, the types of response a patient can have are a complete response (CR), a partial response (PR), progressive disease (PD), and stable disease (SD). | 3 to 6 weeks post-treatment | 
| Patient-reported Quality of Life (QOL) as Assessed by the EORTC QLQ-C30 Scores | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 form is a self-assessment completed by patients which examines current symptoms and functionality. Total score ranges from 0 to 100, a higher score represents a higher (better) quality of life. | Pre-HDRBT, during HDRBT, post HDRBT week 1, week 2, weeks 3-6, 3-6 weeks post-op, every 4 months for 2 years and every 6 months for years 3 and 4 | 
| Patient-reported Quality of Life as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-CR38) Scores | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-CR38 form is a self-assessment completed by patients and examine current symptoms and functionality. Each item is scored from 1 to 4. Total score range is from 38-152. A higher score represents better quality of life. | Pre-HDRBT, during HDRBT, post HDRBT week 1, week 2, weeks 3-6, 3-6 week post-op, every 4 months for 2 years and every 6 months for years 3 and 4 | 
| Patient-reported Quality of Life as Assessed by the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-CR29) Scores | The European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-CR29) form is a self-assessment completed by patients and examine current symptoms and functionality. Each item is scored from 1 to 4. Total score ranges from 29 - 116. A higher score represents better quality of life. | Pre-HDRBT, during HDRBT, post HDRBT week 1, week 2, weeks 3-6, 3-6 week post-op, every 4 months for 2 years and every 6 months for years 3 and 4 | 
| Number of Participants With Acute Gastrointestinal Toxicity Associated With High-Dose-Rate Endorectal Brachytherapy (HDRBT) as Assessed by CTCAE v4.0 | Acute gastrointestinal toxicity will be assessed using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0). CTCAE v4.0 ratings of 3 or 4 (seriousness of 17%) adverse events will be assessed and reported. | 3-6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, high dose endorectal brachytherapy