Colorectal CancerNCT04228614
Evaluation of Somatic Mutation Spectrum as Biomarker for Survival Outcome in Chinese CRC
An observational study of Colorectal Cancer, run by Sun Yat-sen University at 1 site in China.
Trial summary
By analyse the tissue/blood variant spectrum model using NGS, the present clinical trial aims to elucidate the genetic basis of CRC in Chinese; to establish of CRC genetic map in Chinese patients; to identification new genetic biomarkers, drug and pathways; and to subtyping for precision treatment and management for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- How many people
- 1,500 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2018to 1 May 2021
- How long will I take part?
- 3 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients must have baseline evaluations performed prior to the study and must meet all inclusion and exclusion criteria. In addition, the patient of the prospective cohort should be thoroughly informed about the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent. The written informed consent of the prospective cohort should be obtained from the patient prior to enrollment. The following criteria apply to all patients enrolled onto the study unless otherwise specified.
Who may be able to join
- Retrospective cohort:
- The patient had no previous history of tumor prior to the diagnosis of colorectal cancer.
- The tissue samples of patients were obtained from the radical(stage I-III) or palliative (stage IV) resection of colorectal cancer.
- The clinical data of patients are complete.
- The treatment record of the patients after surgery are complete, and the fellow-up data are available.
- Prospective cohort:
Show all 12Show fewer
- Patients who were diagnosed as stage IV colorectal cancer and planed to received palliative systematic chemotherapy.
- Paired 10 ml blood and tissue samples should be available
- The clinical informations of patients and definite pathological diagnosis of colorectal cancer should be obtained
- Patients agree with the group to follow-up them and provide follow-up informations
- Performance status ECOG（Eastern Cooperative Oncology Group） score ≤2
- Informed consent must be obtained from the patient
Who cannot join
- Retrospective cohort:
- The patient had previous history of tumor prior to colorectal cancer surgery
- The clinical data of patients are not available
- 4. The date of treatment after surgery are not integrity, outcome data are not available
- Prospective cohort:
- The patient received a blood transfusion within three months;
Show all 10Show fewer
- The patient has active HIV, hepatitis B or hepatitis C infection;
- pregnant patients;
- Alcohol or drug users;
- Other situation that researchers considered might affect the results of the experiment or violate the ethics.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Medical Oncology,Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Feng Wang, M.D,Ph.D, wangfeng@sysucc.org.cn
Ruihua Xu, M.D,Ph.D
About this study
Official title: A Cohort Study Evaluating the Effectiveness of the Somatic Mutation Spectrum Model in CRC Prognosis and Prediction Stratification
By analyse the tissue/blood variant spectrum model using NGS, the present clinical trial aims to elucidate the genetic basis of CRC in Chinese; to establish of CRC genetic map in Chinese patients; to identification new genetic biomarkers, drug and pathways; and to subtyping for precision treatment and management for Chinese CRC patients.
Read the detailed description
Colorectal cancer (CRC), as one of the common malignant tumors with high morbidity and mortality, is a major health threat in China. Surgical resection is the conventional treatment for early and intermediate stage CRC, chemotherapy is the main treatment for late stage CRC.
Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 170bp, mixed with cell free DNA (cfDNA) of other sources in blood circulation. Although the mechanisms of its release have not been fully addressed, apoptosis and/or necrosis of tumor cells and serum exosome are considered as its main source, which makes it a genomic reservoir of different tumor clones. Also, as its half-life is up to hours, ctDNA is reflecting the most up-to-date status of tumor genome. Hence, it allows for noninvasive molecular characterization of tumors,which can be qualitative, quantitative and used for disease monitoring. The possibility of that ctDNA could be used to detect micrometastatic disease in patients received surgical resection was suggested in several studies. Using Next Generation Sequencing (NGS), Newman et al. have shown that the serum level of ctDNA was correlated with tumor progress and prognosis in NSCLC. Isaac et al. demonstrated the postoperative ctDNA level was associated with breast cancer progression, and it was more sensitive compared to CT scan for predicting the early relapse. Tie et al. examined the postoperative ctDNA level of 1046 plasma samples from a prospective cohort of 230 patients with resected stage II CRC by NGS, and their results demonstrated that recurrence happened in 79% of the patients with positive postoperative ctDNA at median follow-up of 27 months, versus 9.8% in the negative postoperative ctDNA group.
- Conditions
- Colorectal Cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Retrospective cohort | Whole exome sequencing of 2500 retrospective tissue sample. | |
| Prospective cohort | Whole exome sequencing of 500 prospectively collected tissue samples. Panel sequencing of 451 genes of prospectively collected blood samples. |
What is being measured
The primary outcome is the main question the study is designed to answer.
prediction accuracy of survival rate
We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 5 year survival rate of patients is the primary endpoint
Measured: through study completion, an average of 5 years
prediction accuracy of recurrent rate
We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 3 year recurrent rate of patients is the primary endpoint
Measured: through study completion, an average of 3 years
Secondary outcomes (1)
Mutation Consistency of tissue and blood sample
We do NGS sequencing of both the tissue sample and blood sample of the CRC patients. The gene mutation data will be analysis, and the percentage of same and different mutation of tissue and blood sample will be reported.
Measured: through study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start1 May 2018
- Primary completion1 Feb 2020 (estimated)
- Study completion1 May 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen 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
- Other
- Enrolment
- 1,500 participants (estimated)
- Target duration
- 3 Years
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ruihua Xu, Sun Yat-sen University
- Investigators
- Ruihua Xu, MD.,PhD, Study director, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04228614
- Sponsor's protocol ID
- mutation spectrum model-CRC
- Status last verified
- Jan 2020
- First submitted
- 28 Oct 2019
- Last updated
- 18 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12.
PubMed 26457759Rolfo C, Castiglia M, Hong D, Alessandro R, Mertens I, Baggerman G, Zwaenepoel K, Gil-Bazo I, Passiglia F, Carreca AP, Taverna S, Vento R, Santini D, Peeters M, Russo A, Pauwels P. Liquid biopsies in lung cancer: the new ambrosia of researchers. Biochim Biophys Acta. 2014 Dec;1846(2):539-46. doi: 10.1016/j.bbcan.2014.10.001. Epub 2014 Oct 16.
PubMed 25444714Yu SC, Lee SW, Jiang P, Leung TY, Chan KC, Chiu RW, Lo YM. High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing. Clin Chem. 2013 Aug;59(8):1228-37. doi: 10.1373/clinchem.2013.203679. Epub 2013 Apr 19.
PubMed 23603797Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, Shrager JB, Loo BW Jr, Alizadeh AA, Diehn M. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014 May;20(5):548-54. doi: 10.1038/nm.3519. Epub 2014 Apr 6.
PubMed 24705333Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Cheang M, Osin P, Nerurkar A, Kozarewa I, Garrido JA, Dowsett M, Reis-Filho JS, Smith IE, Turner NC. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015 Aug 26;7(302):302ra133. doi: 10.1126/scitranslmed.aab0021.
PubMed 26311728Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.
PubMed 27384348
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cohort Study Evaluating the Effectiveness of the Somatic Mutation Spectrum Model in CRC Prognosis and Prediction Stratification
- ClinicalTrials.gov ID
- NCT04228614
- Acronym / sponsor ID
- mutation spectrum model-CRC
- Conditions
- Colorectal Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 1 Feb 2020 (estimated)
- Study completion
- 1 May 2021 (estimated)
- First posted
- 14 Jan 2020 (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.
By analyse the tissue/blood variant spectrum model using NGS, the present clinical trial aims to elucidate the genetic basis of CRC in Chinese; to establish of CRC genetic map in Chinese patients; to identification new genetic biomarkers, drug and pathways; and to subtyping for precision treatment and management for Chinese CRC patients.
Detailed description
Colorectal cancer (CRC), as one of the common malignant tumors with high morbidity and mortality, is a major health threat in China. Surgical resection is the conventional treatment for early and intermediate stage CRC, chemotherapy is the main treatment for late stage CRC.
Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 170bp, mixed with cell free DNA (cfDNA) of other sources in blood circulation. Although the mechanisms of its release have not been fully addressed, apoptosis and/or necrosis of tumor cells and serum exosome are considered as its main source, which makes it a genomic reservoir of different tumor clones. Also, as its half-life is up to hours, ctDNA is reflecting the most up-to-date status of tumor genome. Hence, it allows for noninvasive molecular characterization of tumors,which can be qualitative, quantitative and used for disease monitoring. The possibility of that ctDNA could be used to detect micrometastatic disease in patients received surgical resection was suggested in several studies. Using Next Generation Sequencing (NGS), Newman et al. have shown that the serum level of ctDNA was correlated with tumor progress and prognosis in NSCLC. Isaac et al. demonstrated the postoperative ctDNA level was associated with breast cancer progression, and it was more sensitive compared to CT scan for predicting the early relapse. Tie et al. examined the postoperative ctDNA level of 1046 plasma samples from a prospective cohort of 230 patients with resected stage II CRC by NGS, and their results demonstrated that recurrence happened in 79% of the patients with positive postoperative ctDNA at median follow-up of 27 months, versus 9.8% in the negative postoperative ctDNA group.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 3 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Retrospective cohort | – | –Whole exome sequencing of 2500 retrospective tissue sample. |
| Prospective cohort | – | –Whole exome sequencing of 500 prospectively collected tissue samples. Panel sequencing of 451 genes of prospectively collected blood samples. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients must have baseline evaluations performed prior to the study and must meet all inclusion and exclusion criteria. In addition, the patient of the prospective cohort should be thoroughly informed about the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent. The written informed consent of the prospective cohort should be obtained from the patient prior to enrollment. The following criteria apply to all patients enrolled onto the study unless otherwise specified.
Key inclusion criteria (12 listed)
- The patient had no previous history of tumor prior to the diagnosis of colorectal cancer.
- The tissue samples of patients were obtained from the radical(stage I-III) or palliative (stage IV) resection of colorectal cancer.
- The clinical data of patients are complete.
- The treatment record of the patients after surgery are complete, and the fellow-up data are available.
- Patients who were diagnosed as stage IV colorectal cancer and planed to received palliative systematic chemotherapy.
Key exclusion criteria (10 listed)
- The patient had previous history of tumor prior to colorectal cancer surgery
- The clinical data of patients are not available
- 4. The date of treatment after surgery are not integrity, outcome data are not available
- The patient received a blood transfusion within three months;
- The patient has active HIV, hepatitis B or hepatitis C infection;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
prediction accuracy of survival rate
Time frame: through study completion, an average of 5 years
We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 5 year survival rate of patients is the primary endpoint
prediction accuracy of recurrent rate
Time frame: through study completion, an average of 3 years
We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 3 year recurrent rate of patients is the primary endpoint
1 secondary outcome
Mutation Consistency of tissue and blood sample
Time frame: through study completion, an average of 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Background: PubMed 26457759Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12.
- Background: PubMed 25444714Rolfo C, Castiglia M, Hong D, Alessandro R, Mertens I, Baggerman G, Zwaenepoel K, Gil-Bazo I, Passiglia F, Carreca AP, Taverna S, Vento R, Santini D, Peeters M, Russo A, Pauwels P. Liquid biopsies in lung cancer: the new ambrosia of researchers. Biochim Biophys Acta. 2014 Dec;1846(2):539-46. doi: 10.1016/j.bbcan.2014.10.001. Epub 2014 Oct 16.
- Background: PubMed 23603797Yu SC, Lee SW, Jiang P, Leung TY, Chan KC, Chiu RW, Lo YM. High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing. Clin Chem. 2013 Aug;59(8):1228-37. doi: 10.1373/clinchem.2013.203679. Epub 2013 Apr 19.
- Background: PubMed 24705333Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, Shrager JB, Loo BW Jr, Alizadeh AA, Diehn M. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014 May;20(5):548-54. doi: 10.1038/nm.3519. Epub 2014 Apr 6.
- Background: PubMed 26311728Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Cheang M, Osin P, Nerurkar A, Kozarewa I, Garrido JA, Dowsett M, Reis-Filho JS, Smith IE, Turner NC. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015 Aug 26;7(302):302ra133. doi: 10.1126/scitranslmed.aab0021.
- Background: PubMed 27384348Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.
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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.
Ruihua Xu, MD.,PhD study director
Sun Yat-sen University
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 Colorectal Cancer, run by Sun Yat-sen University at 1 site in China.
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 12 inclusion and 10 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 18 Jan 2020. 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 China. 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 Feng Wang, MD.,PhD. (+862087343795, wangfeng@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
prediction accuracy of survival rate (time frame: through study completion, an average of 5 years). The study lists 2 primary outcomes in all. 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 NCT04228614, which also lists 6 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 18 Jan 2020; AzTrials last refreshed its copy on 7 Nov 2026.