Colorectal CancerPhase 3SMALLERNCT06520683
Adjuvant PD-1 Blockade for High-risk Stage-II DMMR/MSI-H Colorectal Cancer
A Phase 3 study testing Tislelizumab and Adjuvant chemotherapy in people with Colorectal Cancer and Microsatellite Instability High, run by Sun Yat-sen University at 1 site in China.
Trial summary
This open-label phase III trial investigates the efficacy of two cycles of PD-1 blockade (Tislelizumab) as adjuvant therapy to see how it works compared with standard of care (SOC) in treating patients with stage II dMMR/MSI-H colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colorectal Cancer, Microsatellite Instability High
- What is being tested?
- Tislelizumab and Adjuvant chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2024to 1 Nov 2030
- Phase
- Phase 3
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- dMMR and/or MSI-H colorectal carcinoma that undergo surgical resection
- Pathologically confirmed as stage II (T3-4,N0), with at least one of the following risk factors: 1) T4 (including T4a and T4b); 2) Vascular invasion; 3) Perineural invasion; 4) Poor differentiation (including mucinous and signet-ring carcinoma); 5) Obstruction and/or perforation before surgery.
- Perioperative CT/MR/PET-CT find no signs of metastases
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
- Aged 18-80
- No prior medical therapy (chemotherapy, immunotherapy, biologic or targeted therapy) or radiation therapy for the current cancer
- Adequate organ function
Who cannot join
- Active autoimmune disease that has required systemic treatment in past 2 years
- Positive surgical margin (R1/R2 resection)
- Presence of post-operative complications that may preclude treatment
- Active infection requiring systemic therapy
- Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%.
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
Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651
Guangzhou, Guangdong, 510060
Bin-Yi Xiao, M.D., +86-15800004780, xiaoby@sysucc.org.cn
Pei-Rong Ding, M.D.
About this study
Official title: Short-course PD-1 Blockade As Adjuvant Treatment for High-risk Stage-II DMMR/MSI-H Colorectal Cancer
This open-label phase III trial investigates the efficacy of two cycles of PD-1 blockade (Tislelizumab) as adjuvant therapy to see how it works compared with standard of care (SOC) in treating patients with stage II dMMR/MSI-H colorectal cancer.
The rational of giving PD-1 blockade as adjuvant therapy is based on the fact that tumor recurrence is extremely low among patients receiving neoadjuvant immunotherapy, which suggests that PD-1 blockade may likely improve patients' long-term survival.
As for the short course (two cycles), we have the following considerations: firstly, the NICHE-2 trial, which adopted a two-cycle regimen, reported no recurrences during follow-up, suggesting that short-course anti-PD-1 therapy may be sufficient to improve the survival of patients with localized dMMR/MSI-H colorectal cancer. Secondly, the potential benefits of PD-1 blockade should be balanced against its toxicities, because patients with stage-II dMMR colorectal cancer generally have a good prognosis. Two cycles of PD-1 blockade have been shown to have a good safety profile, with low incidence of grade 3-4 and immune-related adverse events.
Read the detailed description
This is an open-label, multi-centre, randomised, phase III trial comparing the combination of PD-1 blockade + SOC versus SOC alone as adjuvant therapy for patients with high-risk stage-II dMMR/MSI-H colorectal cancer.
Primary Objective: To determine whether the addition of Tislelizumab can significantly improve disease-free survival (DFS) compared to standard of care in patients with high-risk stage-II colorectal cancer.
Secondary objectives:
- To determine whether the addition of Tislelizumab can significantly improve overall survival (OS) compared to standard of care
- To assess the adverse events (AE) profile (including immune-related adverse events, ir-AEs).
OUTLINE: Patients are randomized to 1 of 2 arms, stratified by cT4 status.
Arm 1 (experimental group): patients receive Tislelizumab 200mg intravenously on day 1, with or without adjuvant chemotherapy, and repeat the treatment on day 22. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5.
Arm 2 (control group): patients receive standard of care (SOC), whether with surveillance alone, single-agent Capecitabine, or CapeOx/FOLFOX, at the discretion of the doctor in charge. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5.
Statistics According to the statistical design, 180 patients (90 per arm) are to be randomized. The study is expected to take up to 36 months to complete accrual.
- Conditions
- Colorectal Cancer, Microsatellite Instability High
- Being tested
- Tislelizumab, Adjuvant chemotherapy
- Keywords
- Adjuvant therapy, Stage II CRC, dMMR/MSI-H, PD-1 blockade
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TislelizumabDrug
Also called Tislelizumab (Tevimbra)
- Tislelizumab 200mg (day 1 and day 22), administered after surgery
Adjuvant chemotherapyDrug
- Adjuvant therapy is not mandatory.
- Optional adjuvant regimens include FOLFOX, CapeOX, 5-FU+LV, or Capecitabine.
| Study group | Role | What they receive |
|---|---|---|
| Tislelizumab Arm | Experimental | Two cycles of Tislelizumab 200mg intravenously, on day 1 and day 22, with or without adjuvant chemotherapy Receives: Drug: Tislelizumab; Drug: Adjuvant chemotherapy |
| Control Arm | Active comparator | Receiving standard of Care (either with adjuvant chemotherapy or surveillance alone). Receives: Drug: Adjuvant chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival (DFS)
DFS (tumor-specific) is defined as time from randomization to tumor relapse or tumor-related death. DFS will be compared between treatment arms using the stratified log rank test at one-sided level 0.025. If zero DFS events are observed in a certain stratum at an interim analysis and unstratified log-rank is used, all subsequent analyses for DFS will use unstratified log-rank test.
Measured: 3 years
Secondary outcomes (2)
Overall survival (OS)
OS is defined as time from randomization to death from any cause. Overall survival will be compared between treatment arms using the log-rank test.
Measured: 5 years
Incidence of adverse events
Assessed by Common Terminology Criteria for Adverse Events version 4.0. The overall adverse event rates and the immune-related adverse event rates will be compared between treatment arms using Chi-square test or Fisher's exact test, as appropriate.
Measured: up to 30 days after last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2024
- Study start1 Nov 2024
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- BeiGene
- Responsible party
- Principal investigator, Pei-Rong Ding, Sun Yat-sen University
- Investigators
- Pei-Rong Ding, M.D., Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06520683
- Sponsor's protocol ID
- 2024-FXY-219
- Acronym
- SMALLER
- Status last verified
- Nov 2024
- First submitted
- 20 Jul 2024
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-course PD-1 Blockade As Adjuvant Treatment for High-risk Stage-II DMMR/MSI-H Colorectal Cancer
- ClinicalTrials.gov ID
- NCT06520683
- Acronym / sponsor ID
- SMALLER / 2024-FXY-219
- Conditions
- Colorectal Cancer, Microsatellite Instability High
- Keywords
- Adjuvant therapy, Stage II CRC, dMMR/MSI-H, PD-1 blockade
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- BeiGene
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2030 (estimated)
- First posted
- 25 Jul 2024 (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 open-label phase III trial investigates the efficacy of two cycles of PD-1 blockade (Tislelizumab) as adjuvant therapy to see how it works compared with standard of care (SOC) in treating patients with stage II dMMR/MSI-H colorectal cancer.
The rational of giving PD-1 blockade as adjuvant therapy is based on the fact that tumor recurrence is extremely low among patients receiving neoadjuvant immunotherapy, which suggests that PD-1 blockade may likely improve patients' long-term survival.
As for the short course (two cycles), we have the following considerations: firstly, the NICHE-2 trial, which adopted a two-cycle regimen, reported no recurrences during follow-up, suggesting that short-course anti-PD-1 therapy may be sufficient to improve the survival of patients with localized dMMR/MSI-H colorectal cancer. Secondly, the potential benefits of PD-1 blockade should be balanced against its toxicities, because patients with stage-II dMMR colorectal cancer generally have a good prognosis. Two cycles of PD-1 blockade have been shown to have a good safety profile, with low incidence of grade 3-4 and immune-related adverse events.
Detailed description
This is an open-label, multi-centre, randomised, phase III trial comparing the combination of PD-1 blockade + SOC versus SOC alone as adjuvant therapy for patients with high-risk stage-II dMMR/MSI-H colorectal cancer.
Primary Objective: To determine whether the addition of Tislelizumab can significantly improve disease-free survival (DFS) compared to standard of care in patients with high-risk stage-II colorectal cancer.
Secondary objectives:
- To determine whether the addition of Tislelizumab can significantly improve overall survival (OS) compared to standard of care
- To assess the adverse events (AE) profile (including immune-related adverse events, ir-AEs).
OUTLINE: Patients are randomized to 1 of 2 arms, stratified by cT4 status.
Arm 1 (experimental group): patients receive Tislelizumab 200mg intravenously on day 1, with or without adjuvant chemotherapy, and repeat the treatment on day 22. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5.
Arm 2 (control group): patients receive standard of care (SOC), whether with surveillance alone, single-agent Capecitabine, or CapeOx/FOLFOX, at the discretion of the doctor in charge. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5.
Statistics According to the statistical design, 180 patients (90 per arm) are to be randomized. The study is expected to take up to 36 months to complete accrual.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tislelizumab Arm | Experimental | Drug: Tislelizumab, Drug: Adjuvant chemotherapyTwo cycles of Tislelizumab 200mg intravenously, on day 1 and day 22, with or without adjuvant chemotherapy |
| Control Arm | Active comparator | Drug: Adjuvant chemotherapyReceiving standard of Care (either with adjuvant chemotherapy or surveillance alone). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- dMMR and/or MSI-H colorectal carcinoma that undergo surgical resection
- Pathologically confirmed as stage II (T3-4,N0), with at least one of the following risk factors: 1) T4 (including T4a and T4b); 2) Vascular invasion; 3) Perineural invasion; 4) Poor differentiation (including mucinous and signet-ring carcinoma); 5) Obstruction and/or perforation before surgery.
- Perioperative CT/MR/PET-CT find no signs of metastases
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
- Aged 18-80
Key exclusion criteria (5 listed)
- Active autoimmune disease that has required systemic treatment in past 2 years
- Positive surgical margin (R1/R2 resection)
- Presence of post-operative complications that may preclude treatment
- Active infection requiring systemic therapy
- Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%.
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 |
|---|---|---|
| TislelizumabAlso: Tislelizumab (Tevimbra)- Tislelizumab 200mg (day 1 and day 22), administered after surgery | Drug | Tislelizumab Arm |
| Adjuvant chemotherapy* Adjuvant therapy is not mandatory. * Optional adjuvant regimens include FOLFOX, CapeOX, 5-FU+LV, or Capecitabine. | Drug | Control Arm, Tislelizumab Arm |
Primary outcome
Disease-free survival (DFS)
Time frame: 3 years
DFS (tumor-specific) is defined as time from randomization to tumor relapse or tumor-related death. DFS will be compared between treatment arms using the stratified log rank test at one-sided level 0.025. If zero DFS events are observed in a certain stratum at an interim analysis and unstratified log-rank is used, all subsequent analyses for DFS will use unstratified log-rank test.
2 secondary outcomes
Overall survival (OS)
Time frame: 5 years
Incidence of adverse events
Time frame: up to 30 days after last treatment
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 7 Nov 2024.
- Individual participant dataSharing planned: No
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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.
Pei-Rong Ding, M.D. principal investigator
Sun Yat-Sen University Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tislelizumab and Adjuvant chemotherapy in people with Colorectal Cancer and Microsatellite Instability High, 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 7 inclusion and 5 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 7 Nov 2024. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Bin-Yi Xiao, M.D. (+8615800004780, xiaoby@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival (DFS) (time frame: 3 years). 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 7 Nov 2024.