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

Not Applicable

Completed

Conditions: Rectal Cancer

Interventions: Radiation: High-dose endorectal brachytherapy (HDRBT)

Registration Number: NCT01226979

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HDRBT (High Dose Rectal Brachytherapy)	High-dose endorectal brachytherapy (HDRBT)	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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Pathologic Complete Response	8 weeks	Those participants whose surgical pathology indicated that they had a complete response measured by RECIST. Per Response Evaluation Criteria In Solid Tumors (RECISTv1.0). Complete response (CR) indicating no tumors, a partial (PR) response indicating at least a 30% decrease in tumor diameter (PR), progressive disease (PD) indicating 20% or greater increase in tumor diameter, and stable disease (SD) indicating that the tumor did not shrink significantly to be considered a partial response and did not grow significantly enough to be considered progressive disease.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Response of High-Dose-Rate Endorectal Brachytherapy (HDRBT) Brachytherapy	3 to 6 weeks post-treatment	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. Response Evaluation Criteria In Solid Tumors (RECISTv1.0) is defined as follows: Complete response (CR) indicating no tumors, a partial (PR) response indicating at least a 30% decrease in tumor diameter (PR), progressive disease (PD) indicating 20% or greater increase in tumor diameter, and stable disease (SD) indicating that the tumor did not shrink significantly to be considered a partial response and did not grow significantly enough to be considered progressive disease.
Patient-reported Quality of Life (QOL) as Assessed by the EORTC QLQ-C30 Scores	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	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.
Number of Participants With Acute Gastrointestinal Toxicity Associated With High-Dose-Rate Endorectal Brachytherapy (HDRBT) as Assessed by CTCAE v4.0	3-6 weeks	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.
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	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	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.
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	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	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.