Locally Advanced Rectal CancerNCT04738214
Development of a Genome-based Platform for Personalized Treatment in Locally Advanced Rectal Cancer Patients
An observational study of Locally Advanced Rectal Cancer, run by Yonsei University at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Locally Advanced Rectal Cancer
- What is being tested?
- Neoadjuvant CCRT+operation +/- adjuvant treatment
- How many people
- 39 participants
- Where
- 1 siteSouth Korea
- Study dates
- Feb 2021to 18 Jan 2025
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Yonsei University College of Medicine
Seoul, 03722
Woong Sub Koom, +82-10-8818-1356, MDGOLD@yuhs.ac
About this study
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%.
Read more
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.
Read the detailed description
The treatment in this study is one of the standard treatments suggested by the NCCN guidelines. The patients received operation after neoadjuvant concurrent chemoradiotherapy and pathologic tumor response is evaluated. Before neoadjuvant treatment, the following are obtained; Medical history and physical examination, Tissue acquisition through colonoscopy, Blood Test (CBC), Chemistry Test (SMA), staging through pelvic CT or MRI, PET-CT or chest CT.
Either 5-FU/leucovorin and Capecitabine based concurrent chemoradiotherapy is conducted. The target delineation is performed in 3mm simulation CT for radiotherapy. GTV includes primary lesions ,lymph nodes and mesorectum based on diagnostic CT, MRI, and PET-CT. CTV covers the perirectal and internal pelvic lymph node with microscopic margin of GTV. PTV1 is defined as extending 0.3cm from the GTV. PTV2 is defined as extending 0.5 from CTV. Radiotherapy is performed using 3D conformal radiotherapy, intensity-modulated radiotherapy, volumetric modulated Arc therapy. Radiotherapy is administered daily, five times a week according to the NCCN guidelines. Each treatment is performed with full bladder and prone positioning. Radiotherapy is performed 25 fractions with simultaneous integrated boost method. 2.00Gy is administered for PTV1 while 1.8 Gy is administered for PTV2.
The operation is performed 5-12 weeks after CCRT. If the patients refuse, physicians do not perform surgery and undergo wait-and-see. The treatment response is evaluated based on standard treatment process. During the treatment, the regular check up is conducted to evaluate the acute toxicity regarding treatment.
The acquired specimens are used for RNA sequencing and organoid construction. The RNA sequencing is used to analyze the differentially expressed based on treatment response to neoadjuvant concurrent chemoradiotherapy.
- Conditions
- Locally Advanced Rectal Cancer
- Being tested
- Neoadjuvant CCRT+operation +/- adjuvant treatment
- Keywords
- Rectal cancer, Personalized treatment, Genome-based platform, preoperative chemoradiotherapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant CCRT+operation +/- adjuvant treatmentOther
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic response rate
The rate of patients who achieved complete response or partial response after concurrent chemoradiotherapy
Measured: up to 2 year
Secondary outcomes (1)
Disease free survival
The rate of patients without disease or death after treatment
Measured: up to 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2021
- Study startFeb 2021 (estimated)
- Primary completion18 Jan 2025 (estimated)
- Study completion18 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Rectal CancerStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 39 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Woong Sub Koom, Principal investigator, Severance Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04738214
- Sponsor's protocol ID
- 4-2020-1342
- Status last verified
- Jan 2021
- First submitted
- 29 Jan 2021
- Last updated
- 4 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Research related documents will be stored in a file with a separate password under the responsibility of the lead researcher and stored in a locked laboratory. These research-related records will be kept for 3 years from the time the research is completed, and after that, the research team will discard the documents. Tissue samples obtained from patients are subjected to genome analysis by extracting RNA and DNA. Patient registration information is encrypted and stored separately, and stored in freezer at -80°C until experimentation at Yonsei University Medical Research Institute under the supervision of the research director.
Publications
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.
PubMed 28881920Martens 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.
PubMed 27509881Scott 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.
PubMed 27993569
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of a Genome-based Platform for Personalized Treatment in Locally Advanced Rectal Cancer Patients
- ClinicalTrials.gov ID
- NCT04738214
- Acronym / sponsor ID
- 4-2020-1342
- Conditions
- Locally Advanced Rectal Cancer
- Keywords
- Rectal cancer, Personalized treatment, Genome-based platform, preoperative chemoradiotherapy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- Feb 2021 (estimated)
- Primary completion
- 18 Jan 2025 (estimated)
- Study completion
- 18 Jan 2025 (estimated)
- First posted
- 4 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The treatment in this study is one of the standard treatments suggested by the NCCN guidelines. The patients received operation after neoadjuvant concurrent chemoradiotherapy and pathologic tumor response is evaluated. Before neoadjuvant treatment, the following are obtained; Medical history and physical examination, Tissue acquisition through colonoscopy, Blood Test (CBC), Chemistry Test (SMA), staging through pelvic CT or MRI, PET-CT or chest CT.
Either 5-FU/leucovorin and Capecitabine based concurrent chemoradiotherapy is conducted. The target delineation is performed in 3mm simulation CT for radiotherapy. GTV includes primary lesions ,lymph nodes and mesorectum based on diagnostic CT, MRI, and PET-CT. CTV covers the perirectal and internal pelvic lymph node with microscopic margin of GTV. PTV1 is defined as extending 0.3cm from the GTV. PTV2 is defined as extending 0.5 from CTV. Radiotherapy is performed using 3D conformal radiotherapy, intensity-modulated radiotherapy, volumetric modulated Arc therapy. Radiotherapy is administered daily, five times a week according to the NCCN guidelines. Each treatment is performed with full bladder and prone positioning. Radiotherapy is performed 25 fractions with simultaneous integrated boost method. 2.00Gy is administered for PTV1 while 1.8 Gy is administered for PTV2.
The operation is performed 5-12 weeks after CCRT. If the patients refuse, physicians do not perform surgery and undergo wait-and-see. The treatment response is evaluated based on standard treatment process. During the treatment, the regular check up is conducted to evaluate the acute toxicity regarding treatment.
The acquired specimens are used for RNA sequencing and organoid construction. The RNA sequencing is used to analyze the differentially expressed based on treatment response to neoadjuvant concurrent chemoradiotherapy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- 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
- Performance status 0 or 1 based on ECOG
- Patients agreed to provide the tissue sample
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neoadjuvant CCRT+operation +/- adjuvant treatmentPatients 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. | Other | – |
Primary outcome
Pathologic response rate
Time frame: up to 2 year
The rate of patients who achieved complete response or partial response after concurrent chemoradiotherapy
1 secondary outcome
Disease free survival
Time frame: up to 2 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Background: PubMed 28881920Glynne-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.
- Background: PubMed 27509881Martens 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.
- Background: PubMed 27993569Scott 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.
- Individual participant dataSharing planned: No. Research related documents will be stored in a file with a separate password under the responsibility of the lead researcher and stored in a locked laboratory. These research-related records will be kept for 3 years from the time the research is completed, and after that, the research team will discard the documents. Tissue samples obtained from patients are subjected to genome analysis by extracting RNA and DNA. Patient registration information is encrypted and stored separately, and stored in freezer at -80°C until experimentation at Yonsei University Medical Research Institute under the supervision of the research director.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Woong Sub Koom principal investigator
Severance Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Locally Advanced Rectal Cancer, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Woong Sub Koom (+82-10-8818-1356, MDGOLD@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic response rate (time frame: up to 2 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04738214, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.