Development of a Genome-based Platform for Personalized Treatment in Locally Advanced Rectal Cancer Patients

NCT04738214 | Unknown DMC

• 1 other identifier: 4-2020-1342
• Study Type: observational
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This study is aimed to develop a genome-based platform to predict patients who can achieve pathologic complete response after neoadjuvant treatment in locally advanced rectal cancer. The main treatments for locally advanced rectal cancer is surgical removal such as lower anterior resection after neoadjuvant CCRT. About 10-40% of patients showed pathologic complete response after neoadjuvant CCRT. Mandard tumor regression grade (TRG) is used to grade the histologic tumor response after neoadjuvant treatment. TRG 1 represents the pathologic complete response and TRG2 as histologically small group of cancer cells. Accordingly, TRG1 and 2 are expressed as good responder. Even though the surgery is being performed as an essential treatment, there are various surgery-related sequelae such as colostomy. Also, in some patients, surgery may be refused or surgery may not be performed due to an underlying disease. About 15-20% of local recurrence was reported in patients who did not undergo surgery and the 3-year survival rate was 96.6%. Colorectal cancer genetically can be divided into 4-subtypes. With the recent development of genome testing technology, genome analysis has been actively conducted in colorectal cancer. The most commonly known genetic subtype of colorectal cancer is classified into a total of 4 types as consensus molecular subtype (CMS); CMS1, CMS2, CMS3, CMS4. However, this was analyzed in colorectal cancer patients who did not undergo radiotherapy. There is no data regarding the response to radiation therapy according to each genetic subtype. Therefore, classifying the subtypes through genomic analysis and studying the responsiveness to radiotherapy in each subtype is needed. In this study, we aimed to develop a platform that predicts pathologic tumor response after CCRT based on genomic information. Furthermore, being able to select patients who can wait-and-see without surgery using platform.

Conditions

Locally Advanced Rectal Cancer

Keywords

Rectal cancer, Personalized treatment, Genome-based platform, preoperative chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Pathologic response rate

  The rate of patients who achieved complete response or partial response after concurrent chemoradiotherapy

  up to 2 year

Secondary Outcomes (1)

• Disease free survival

  up to 2 year

Interventions

Neoadjuvant CCRT+operation +/- adjuvant treatment OTHER

Patients receive neoadjuvant CCRT and operation. Adjuvant treatment after operation is performed depending on pathologic response. The patients showing pathologic complete response after neoadjuvant CCRT are not treated with any adjuvant treatment.

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with locally advanced rectal cancer are subject to this trial. The patients undergo endoscopic biopsy and receive neoadjuvant CCRT and surgery. In case that pathologic CR status obtained after CCRT, no additional treatment is performed. Patients without pathologic CR status are treated with adjuvant treatment.

You may qualify if:

• Patients older than 19 years old
• Clinically or histologically diagnosed rectal cancer (adenocarcinoma)
• Patients who satisfy all of the following conditions with either rectal cancer stage T3-4 or T2 in lower rectal cancer with any N stage according to 8th edition of American Joint Committee on Cancer
• \- Stage T3-4 (T2 in lower rectum) in CT or MRI
• Performance status 0 or 1 based on ECOG
• Patients agreed to provide the tissue sample
• Diseases can be evaluated according to RECIST Version 1.1
• Patients who voluntarily agreed to informed consent

You may not qualify if:

• Patients with distant metastasis
• Patients with uncontrolled viral infection (HIV, HBV, HCV)
• Patient who are pregnant, or have possibility of pregnancy and are on lactating
• Hypersensitivity or history of allergic to the drug being used
• Patients with cerebrovascular disease, complications, and infections that are not medically controlled
• Patients with history of other malignant diseases within the past 5 years (excluding cured non-melanoma skin cancer or in situ cervical cancer)
• Those who are taking drugs that can cause drug interactions with chemotherapy
• Patients who withdraw consent

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University College of Medicine

Seoul, 03722, South Korea

Location

Related Publications (3)

• Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rodel C, Cervantes A, Arnold D; ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40. doi: 10.1093/annonc/mdx224. No abstract available.

  PMID: 28881920 BACKGROUND

• Martens MH, Maas M, Heijnen LA, Lambregts DM, Leijtens JW, Stassen LP, Breukink SO, Hoff C, Belgers EJ, Melenhorst J, Jansen R, Buijsen J, Hoofwijk TG, Beets-Tan RG, Beets GL. Long-term Outcome of an Organ Preservation Program After Neoadjuvant Treatment for Rectal Cancer. J Natl Cancer Inst. 2016 Aug 10;108(12):djw171. doi: 10.1093/jnci/djw171. Print 2016 Dec.

  PMID: 27509881 BACKGROUND

• Scott JG, Berglund A, Schell MJ, Mihaylov I, Fulp WJ, Yue B, Welsh E, Caudell JJ, Ahmed K, Strom TS, Mellon E, Venkat P, Johnstone P, Foekens J, Lee J, Moros E, Dalton WS, Eschrich SA, McLeod H, Harrison LB, Torres-Roca JF. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol. 2017 Feb;18(2):202-211. doi: 10.1016/S1470-2045(16)30648-9. Epub 2016 Dec 18.

  PMID: 27993569 BACKGROUND

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Woong Sub Koom

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Woong Sub Koom

CONTACT

+82-10-8818-1356; MDGOLD@yuhs.ac

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 4, 2021
• Study Start: February 1, 2021
• Primary Completion: January 18, 2025
• Study Completion: January 18, 2025
• Last Updated: February 4, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)