Rectal Cancer Stage IIIPhase 4NCT05148767
UGT1A1-Based Irinotecan Therapy for Locally Advanced Rectal Cancer
A Phase 4 study testing Neoadjuvant chemoradiotherapy based on irinotecan in people with Rectal Cancer Stage III, run by Zhejiang Cancer Hospital at 1 site in China.
Trial summary
To explore whether the application of irinotecan under the guidance of UGT1A1 gene in neoadjuvant chemotherapy and radiotherapy for locally advanced rectal cancer could improve the clinical efficacy in the real world. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer Stage III
- What is being tested?
- Neoadjuvant chemoradiotherapy based on irinotecan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 606 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2022to 30 Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed rectal adenocarcinoma
- Clinical stage T3-4 and / or Nude positive, and the treatment plan is nCRT.
- Without distance metastases
- A need for tumor withdrawal.
- Aged 18-75 years old, regardless of gender.
- ECOG score 0-2.
Show all 9Show fewer
- Detection of UGT1A1*6 and * 28 gene status.
- Be able to comply with the plan during the study period.
- Sign the inform consent
Who cannot join
- Pregnant or breastfeeding women
- Those with other history of malignant disease in the past 5 years, except for cured skin cancer and cervical carcinoma in situ
- If there is an uncontrolled history of epilepsy, central nervous system disease or mental disorder, the investigator may determine that the clinical severity may hinder the signing of informed consent or affect the patient's oral medication compliance.
- Clinically severe (ie, active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure or severe arrhythmia requiring medication intervention (see appendix 12), or a history of myocardial infarction in the last 12 months
- Organ transplantation requires immunosuppressive therapy Severe uncontrolled recurrent infections, or other serious uncontrolled concomitant diseases
- Subject blood routine and biochemical indicators do not meet the following criteria: hemoglobin ≥ 90g / L; absolute neutrophil count (ANC) ≥ 1.5 × 109 / L; Alanine transaminase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal; alkaline phosphatase (ALP) ≤2.5 times the normal upper limit; serum total bilirubin <1.5 times the normal upper limit; serum creatinine <1 times the normal upper limit; serum albumin ≥ 30g / L
- Anyone who is allergic to any research medication
- DPD deficiency
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Zhejiang Cancer Hospital
Hangzhou, Zhejiang
Ji Zhu, MD, 571-88128142 ext. +86, leo.zhu@126.com
Quanquan Sun, MD, 571-88128212 ext. +86, sunqq@zjcc.org.cn
About this study
Official title: Neoadjuvant Chemoradiation With Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer: A Real-Word Multi-center Study
To explore whether the application of irinotecan under the guidance of UGT1A1 gene in neoadjuvant chemotherapy and radiotherapy for locally advanced rectal cancer could improve the clinical efficacy in the real world.
Read the detailed description
Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is the standard care of treatment for locally advanced rectal cancer (LARC), which could effectively reduce the risk of local recurrence, increase the chance of sphincter preservation, and effectively improve the quality of life of patients. However, only about 8% of patients can benefit from nCRT. Therefore, to improve the therapeutic effect of nCRT and retain the organ function of patients so as to improve their quality of life is the focus of the current investigation.
In the previous study, the investigator have completed a series of clinical researches of irinotecan guided by UGT1A1 gene for nCRT in rectal cancer. A dose climbing study was firstly conducted to explore the maximum tolerable dose of irinotecan for nCRT in rectal cancer. The results indicated that the weekly dose intensity of irinotecan could be increased from 50mg/m2 to 80mg/m2 when the genotype of UGT1A1*28 locus was 6/6, and the weekly dose intensity of irinotecan could also reach 65mg/m2 when the genotype of irinotecan was 6/7 phenotype. Further analysis also demonstrated that there was a dose-effect relationship between the total dose of irinotecan and pathological complete remission (pCR). The recently published CinClare study is a 3-phase randomized controlled trial that doubles the pCR rate and the total CR rate in combination with irinotecan on the basis of capecitabine combined with radiotherapy. However, in the Aristotle study conducted in the United Kingdom at the same phase, it has not been proved that irinotecan could improve the pCR rate, and it is not known whether the difference between the two studies is completely attributed to the irinotecan dose. Therefore, the investigator designed this real-world study to explore whether irinotecan can indeed improve the treatment efficacy in the real world when using irinotecan under the guidance of UGT1A1 gene in nCRT for LARC. Any locally advanced rectal cancer patients treated with irinotecan-based neoadjuvant radiotherapy and chemotherapy can be enrolled in this study. It is expected that the results of this study could provide more basis for individualized treatment of LARC.
- Conditions
- Rectal Cancer Stage III
- Being tested
- Neoadjuvant chemoradiotherapy based on irinotecan
- Keywords
- locally advanced rectal cancer, Neoadjuvant chemoradiotherapy, irinotecan
- 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 chemoradiotherapy based on irinotecanDrug
Patients with locally advanced rectal cancer treated with irinotecan-based chemoradiotherapy were enrolled in this study. The dose of irinotecan is determined by the genotype of UGT1A1.Concurrent Chemoradiotherapy:
Radiation: 50Gy/25Fx; Capecitabine: 625mg/m2 bid Monday-Friday per week; Irinotecan: 80mg/m2 (UGT1A1*28 and *6: 6/6+GG) or 65mg/m2 (UGT1A1*28 and *6 ：6/7+GG or 6/6+GA) or 50mg/m2 （UGT1A1*28 and *6 ：7/7+GG or 6/6+AA or 6/7+GA）.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant chemoradiotherapy based on irinotecan | Experimental | Locally advanced rectal cancer patients who were treated with irinotecan-based neoadjuvant chemoradiotherapy regimen can be enrolled in this group. Receives: Drug: Neoadjuvant chemoradiotherapy based on irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission rate
The tumor disappeared completely and the tumor markers remained normal for at least 4 weeks.
Measured: 3 months after neoadjuvant chemoradiotherapy
Locally recurrence rate
The proportion of recurrent rectal tumors in the total population after the complete regression of rectal tumors
Measured: Within 5 years after the end of treatment
DFS
The time from complete regression of the tumor after neoadjuvant therapy or radical resection to the first recurrence or death
Measured: Within 5 years after the end of treatment
OS
The time from enrolled in the study to death caused by any cause
Measured: Within 5 years after the end of treatment
Toxicity effect
Any adverse reactions caused by neoadjuvant chemoradiotherapy or surgery
Measured: Within 5 years after the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2021
- Study start1 Jan 2022 (estimated)
- Primary completion1 Jun 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal Cancer Stage IIIStudies of the same condition, open and under way.
- More trials run by Zhejiang Cancer HospitalThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 606 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ji Zhu, MD, Zhejiang Cancer Hospital
- Investigators
- Ji Zhu, MD, Principal investigator, Zhejiang Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05148767
- Sponsor's protocol ID
- CARTOnG-2003
- Status last verified
- Dec 2021
- First submitted
- 7 Oct 2021
- Last updated
- 8 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Chemoradiation With Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer: A Real-Word Multi-center Study
- ClinicalTrials.gov ID
- NCT05148767
- Acronym / sponsor ID
- CARTOnG-2003
- Conditions
- Rectal Cancer Stage III
- Keywords
- locally advanced rectal cancer, Neoadjuvant chemoradiotherapy, irinotecan
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 606 participants (estimated)
- Lead sponsor
- Zhejiang Cancer HospitalUniversity, hospital or other
- Study start
- 1 Jan 2022 (estimated)
- Primary completion
- 1 Jun 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 8 Dec 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.
To explore whether the application of irinotecan under the guidance of UGT1A1 gene in neoadjuvant chemotherapy and radiotherapy for locally advanced rectal cancer could improve the clinical efficacy in the real world.
Detailed description
Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is the standard care of treatment for locally advanced rectal cancer (LARC), which could effectively reduce the risk of local recurrence, increase the chance of sphincter preservation, and effectively improve the quality of life of patients. However, only about 8% of patients can benefit from nCRT. Therefore, to improve the therapeutic effect of nCRT and retain the organ function of patients so as to improve their quality of life is the focus of the current investigation.
In the previous study, the investigator have completed a series of clinical researches of irinotecan guided by UGT1A1 gene for nCRT in rectal cancer. A dose climbing study was firstly conducted to explore the maximum tolerable dose of irinotecan for nCRT in rectal cancer. The results indicated that the weekly dose intensity of irinotecan could be increased from 50mg/m2 to 80mg/m2 when the genotype of UGT1A1*28 locus was 6/6, and the weekly dose intensity of irinotecan could also reach 65mg/m2 when the genotype of irinotecan was 6/7 phenotype. Further analysis also demonstrated that there was a dose-effect relationship between the total dose of irinotecan and pathological complete remission (pCR). The recently published CinClare study is a 3-phase randomized controlled trial that doubles the pCR rate and the total CR rate in combination with irinotecan on the basis of capecitabine combined with radiotherapy. However, in the Aristotle study conducted in the United Kingdom at the same phase, it has not been proved that irinotecan could improve the pCR rate, and it is not known whether the difference between the two studies is completely attributed to the irinotecan dose. Therefore, the investigator designed this real-world study to explore whether irinotecan can indeed improve the treatment efficacy in the real world when using irinotecan under the guidance of UGT1A1 gene in nCRT for LARC. Any locally advanced rectal cancer patients treated with irinotecan-based neoadjuvant radiotherapy and chemotherapy can be enrolled in this study. It is expected that the results of this study could provide more basis for individualized treatment of LARC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant chemoradiotherapy based on irinotecan | Experimental | Drug: Neoadjuvant chemoradiotherapy based on irinotecanLocally advanced rectal cancer patients who were treated with irinotecan-based neoadjuvant chemoradiotherapy regimen can be enrolled in this group. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Pathologically confirmed rectal adenocarcinoma
- Clinical stage T3-4 and / or Nude positive, and the treatment plan is nCRT.
- Without distance metastases
- A need for tumor withdrawal.
- Aged 18-75 years old, regardless of gender.
Key exclusion criteria (8 listed)
- Pregnant or breastfeeding women
- Those with other history of malignant disease in the past 5 years, except for cured skin cancer and cervical carcinoma in situ
- If there is an uncontrolled history of epilepsy, central nervous system disease or mental disorder, the investigator may determine that the clinical severity may hinder the signing of informed consent or affect the patient's oral medication compliance.
- Clinically severe (ie, active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure or severe arrhythmia requiring medication intervention (see appendix 12), or a history of myocardial infarction in the last 12 months
- Organ transplantation requires immunosuppressive therapy Severe uncontrolled recurrent infections, or other serious uncontrolled concomitant diseases
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 chemoradiotherapy based on irinotecanPatients with locally advanced rectal cancer treated with irinotecan-based chemoradiotherapy were enrolled in this study. The dose of irinotecan is determined by the genotype of UGT1A1.Concurrent Chemoradiotherapy: Radiation: 50Gy/25Fx; Capecitabine: 625mg/m2 bid Monday-Friday per week; Irinotecan: 80mg/m2 (UGT1A1*28 and *6: 6/6+GG) or 65mg/m2 (UGT1A1*28 and *6 ：6/7+GG or 6/6+GA) or 50mg/m2 （UGT1A1*28 and *6 ：7/7+GG or 6/6+AA or 6/7+GA）. | Drug | Neoadjuvant chemoradiotherapy based on irinotecan |
Primary outcome
Complete remission rate
Time frame: 3 months after neoadjuvant chemoradiotherapy
The tumor disappeared completely and the tumor markers remained normal for at least 4 weeks.
Locally recurrence rate
Time frame: Within 5 years after the end of treatment
The proportion of recurrent rectal tumors in the total population after the complete regression of rectal tumors
DFS
Time frame: Within 5 years after the end of treatment
The time from complete regression of the tumor after neoadjuvant therapy or radical resection to the first recurrence or death
OS
Time frame: Within 5 years after the end of treatment
The time from enrolled in the study to death caused by any cause
Toxicity effect
Time frame: Within 5 years after the end of treatment
Any adverse reactions caused by neoadjuvant chemoradiotherapy or surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2021.
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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.
Ji Zhu, MD principal investigator
Zhejiang Cancer Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Neoadjuvant chemoradiotherapy based on irinotecan in people with Rectal Cancer Stage III, run by Zhejiang Cancer Hospital 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 9 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: looking for participants now, as of the sponsor's last update on 8 Dec 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 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ji Zhu, MD (571-88128142 ext. +86, leo.zhu@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission rate (time frame: 3 months after neoadjuvant chemoradiotherapy). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Dec 2021.