Evaluation of Efficacy, Quality of Life and Cost Effectiveness of Short-course Radiotherapy Followed by Capecitabine Plus Oxaliplatin chemotheRapy and TME for High-risk Rectal Cancer (ESCORT Trial)

Multimodality treatment including surgery and radiotherapy is the current standard of care in locally advanced rectal cancer. Most clinical trials comparing short course radiotherapy (SCRT) with long course chemoradiotherapy(LCRT) did not find significant differences in oncological outcomes and short-term outcomes even though some debates. Recently, Stockholm III trial comparing SCRT plus delayed surgery with SCRT plus immediate surgery and LCRT demonstrated no differences with respect to short-term outcomes such as complications, mortality, and acute toxicity. However, overall quality of life (QoL) after curative treatment for rectal cancer is still major concern in both SCRT and LCRT. Furthermore, daily hospital visits for 5 weeks may be the cause of the increase of total medical cost due to indirect medical expense in patients with LCRT, especially in rural area. SCRT plus chemotherapy followed by delayed surgery may have the possibility of reducing total hospital costs as well as increasing QoL by proving non-inferiority in terms of perioperative outcomes. The present prospective single-arm phase 2 trial was designed to validate the efficacy, quality of life and cost effectiveness of preoperative short-course radiotherapy plus XELOX chemotherapy followed by delayed surgery for high-risk rectal cancer patient based on magnetic resonance imaging.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Radiation: preoperative short-course radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 31
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Min Soo Cho, MD; Phone Number: 82-2-2228-2107; Email: nagase96@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • The Division of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine
    • Contact: Min Soo Cho, MD; Phone Number: 82-2-2228-2107; Email: nagase96@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. High-risk patients of rectal cancer on pretreatment MRI using the following risk stratification system Location of the lower part of the tumor is measured below less than 10 cm on the anal verge and lower part of the tumor is located below the lower limit of the peritoneal reflection.

   If there is more than one, classify as a high risk group Positive CRM threatening: 5mm ≦ Extramural depth Positive EMVI.

   cN2: Positive Lateral pelvic LN metastasis

2. Between 19 and 80 years of age;
3. Satisfactory performance status: ECOG≦2
4. American Society of Anesthesiologists (ASA) physical status classification system class I~III
5. Adequate hematologic function: white blood cell(WBC) counts≥4,000/mm3, neutrophils counts ≥ 1,500/mm3, platelet counts ≥ 100,000/µL, hemoglobin ≥ 9g/L;
6. Adequate renal function: creatinine ≤ 1.5×upper normal limit

Exclusion Criteria:

1. The evidence of relapse of distant metastasis
2. Receiving treatment of other anti-cancer drug or methods
3. Patients have low compliance and are not able to complete the entire trial
4. Presence of uncontrolled life-threatening diseases
5. cT4 with infiltration of anterior organ on pretreatment MRI
6. cT4 with infiltration of internal or external anal sphincter on pretreatment MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative short-course radiotherapy; 1-week short-course radiation (5 Gy x 5) plus 6-week XELOX (capecitabine 1,000mg/m2 and oxaliplatin 130mg/m2 every 3 weeks) chemotherapy before total mesorectal excision (TME)	Radiation: preoperative short-course radiotherapy; 1-week short-course radiation (5 Gy x 5) plus 6-week XELOX (capecitabine 1,000mg/m2 and oxaliplatin 130mg/m2 every 3 weeks) chemotherapy before total mesorectal excision (TME)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathologic complete response (pCR) rate	According to pathological response criteria, a total regression is considered a complete response	Two weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute toxicities during radiation and chemotherapy	Incidence of acute toxicities during radiation and chemotherapy	Three months
Incidence of surgical complications	Incidence of surgical complications	Four weeks after surgery
Quality of life	QOL assessed using EORTC QLQ-CR29 survey form. The EORTC QLQ-CR29 is a 29-item colon and rectum cancer site-specific supplemental module that aims to enhance the sensitivity and specificity for colorectal cancer quality of life measures. The original English version comprises 4 multi-item scales (body image, urinary frequency, blood and mucus in stool, and stool frequency) and 17 functional/symptomatic single-items(anxiety, weight, sexual interest, urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problem, impotence or dyspareunia), with higher scores indicating better functional or worse symptomatic status. Of these 21 scales or items, only body image, anxiety, weight, and sexual interest are functional domain scales/items, and all the remaining are symptomatic.	Baseline and QOL at 8 weeks after radiotherapy
Cost effectiveness	QALYs (quality adjusted life years) with treatment protocol	Three months

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2019
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: August 30, 2018
• First Submitted That Met QC Criteria: September 17, 2018
• First Posted (Actual): September 18, 2018

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 12, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: 4-2018-0612

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No