Colorectal CancerPhase 2NCT06099951
Total Neoadjuvant Treatment for pMMR Locally Advanced Low Rectal Cancer: Anti-PD-1 Antibody With FOLFOXIRI and Preoperative Radiation Therapy
A Phase 2 study testing Serplulimab + FOLFOXIRI and Radiation therapy in people with Colorectal Cancer, run by Sun Yat-sen University.
Trial summary
For locally advanced rectal cancer, the initial goal of neoadjuvant chemoradiotherapy is to reduce local recurrence, but the pathologic complete response (PCR) rate is low, and distant metastasis becomes the main treatment failure pattern. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Serplulimab + FOLFOXIRI and Radiation therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2023to 1 Sep 2027
- Phase
- Phase 2
- 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
- The pathological confirmation is rectal adenocarcinoma. Additionally, the tumor biopsy immunohistochemistry indicates pMMR, with all MSH1, MSH2, MSH6, and PMS2 showing positive expression.
- Age: 18 to 75 years old,allgenders
- MRI examination confirms that the lower margin of the tumor is within 5cm from the anal verge.
- Clinical stage cT3-4N0M0 or cTxN+M0, with or without positive MRF, with or without positive EMVI, estimated to be eligible for R0 resection.
- No signs of intestinal obstruction before surgery; or resolution of obstruction after proximal colostomy surgery
- Performance status (ECOG score) ≤ 2
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- Hematology: WBC > 3 × 10^9 / L; PLT > 80 × 10^9 / L; Hb > 90 g/L;
- Liver function: ALT and AST ≤ 2.5 × ULN; bilirubin ≤ 1.5 × ULN;
- Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCr) ≥ 60 ml/min;
- Signed informed consent, willingness to undergo treatment according to this protocol, and good compliance with medication.
- No history of prior surgery, chemotherapy, radiation therapy, or immunotherapy.
Who cannot join
- Co-existing with other serious illnesses, including severe electrolyte disorders, bleeding tendencies, etc.
- Active or uncontrolled severe infections: a) Known human immunodeficiency virus (HIV) infection. b) Known clinically significant liver disease history, including viral hepatitis [known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (>1×104 copies/mL or >2000 IU/mL)]. c) Known hepatitis C virus (HCV) infection with positive HCV RNA (>1×103 copies/mL), or other hepatitis, liver cirrhosis.
- Women who are pregnant or breastfeeding and have childbearing potential but are not taking adequate contraceptive measures.
- Patients with severe brain disorders or mental illnesses (such as depression, mania, obsessive-compulsive disorder, and schizophrenia) that affect the patient's ability to self-report.
- Patients with autoimmune diseases, blood system disorders, and a history of organ transplantation, long-term use of steroids, or immunosuppressive agents
- History of other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ or basal cell carcinoma of the skin.
- History of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation).
- Hypertension that cannot be well controlled with antihypertensive medications (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Single Arm Phase II Clinical Trial of Recombinant Humanized Anti PD-1 Monoclonal Antibody and FOLFOXIRI Regimen Combined With Preoperative Intensity Modulated Radiation Therapy as the Total Neoadjuvant Treatment for pMMR Locally Advanced Low Rectal Cancer
For locally advanced rectal cancer, the initial goal of neoadjuvant chemoradiotherapy is to reduce local recurrence, but the pathologic complete response (PCR) rate is low, and distant metastasis becomes the main treatment failure pattern. With the gradual optimization of neoadjuvant chemotherapy regimens, the tumor regression efficacy in patients has improved, leading to increased organ preservation and reduced distant metastasis. Therefore, neoadjuvant treatment for locally advanced rectal cancer has transitioned from an era focused on local control of recurrence to an era focused on improving tumor regression, organ preservation, and long-term survival. Thus, there is a trend towards intensifying the whole course of neoadjuvant treatment for rectal cancer to preserve organ function. The combination of chemotherapy, immunotherapy, and radiotherapy is currently the most powerful approach to maximize tumor regression and achieve organ preservation in low rectal cancer. Currently, several clinical studies on the use of PD-1 inhibitors in combination with preoperative chemoradiotherapy for locally advanced rectal cancer are ongoing internationally, with the majority focusing on PD-1 monotherapy or PD-1 combined with the CapOX regimen in combination with synchronous chemoradiotherapy as neoadjuvant treatment. However, there is no specific research reported on the use of PD-1 combined with FOLFOXIRI regimen in combination with synchronous chemoradiotherapy as a whole course neoadjuvant treatment for pMMR (proficient mismatch repair) locally advanced rectal cancer. Based on the above evidence from evidence-based medicine, we plan to conduct a phase II prospective clinical study to explore the efficacy and treatment safety of PD-1 monoclonal antibody and FOLFOXIRI chemotherapy combined with intensity-modulated radiotherapy as a whole course neoadjuvant treatment in pMMR locally advanced low rectal cancer. The results of this study may open up new treatment approaches for optimizing whole course neoadjuvant chemotherapy in locally advanced rectal cancer and provide a novel treatment strategy for organ preservation in pMMR rectal cancer.
- Conditions
- Colorectal Cancer
- Being tested
- Serplulimab + FOLFOXIRI, Radiation therapy
- Keywords
- Colorectal cancer, Neoadjuvant chemoradiotherapy, Neoadjuvant immunotherapy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Serplulimab + FOLFOXIRIDrug
Starting from day 0, the patient will receive 8 cycles of FOLFOXIRI regimen at specific intervals. The FOLFOXIRI regimen includes irinotecan 165mg/m2, oxaliplatin 85mg/m2, calcium folinate 200mg/m2 on day 1, followed by continuous intravenous infusion of 5-FU 2400mg/m2/day for 46 hours. This regimen is repeated every 14 days.During radiotherapy (Monday to Friday), the patient will receive capecitabine 1650mg/m2/day orally twice daily. Serplulimab immunotherapy will be administered every 2 weeks during the FOLFOXIRI neoadjuvant chemotherapy period. Serplulimab will be given on the first day and the 14th day of radiotherapy, dissolved in 100ml normal saline and administered intravenously over 30-60 minutes at a dose of 200mg.
Radiation therapyRadiation
Radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Serplulimab+FOLFOXIRI | Experimental | Not described Receives: Drug: Serplulimab + FOLFOXIRI; Radiation: Radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete tumor response rate.
Including pathological complete response (pCR) and clinical complete response (cCR); pathological complete response is defined as the absence of visible tumor cells in the rectal specimen obtained during surgery
Measured: Immediately After obtaining the surgical specimen.
Secondary outcomes (1)
Sphincter preservation rate
Rate of patients preserving the anal sphincter during surgery
Measured: During surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2023
- Study start1 Nov 2023 (estimated)
- Primary completion1 Sep 2024 (estimated)
- Study completion1 Sep 2027 (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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ZHI-ZHONG PAN, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06099951
- Sponsor's protocol ID
- 2023-FXY-173-Department of CRC
- Status last verified
- Oct 2023
- First submitted
- 20 Oct 2023
- Last updated
- 25 Oct 2023
- 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 25 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Arm Phase II Clinical Trial of Recombinant Humanized Anti PD-1 Monoclonal Antibody and FOLFOXIRI Regimen Combined With Preoperative Intensity Modulated Radiation Therapy as the Total Neoadjuvant Treatment for pMMR Locally Advanced Low Rectal Cancer
- ClinicalTrials.gov ID
- NCT06099951
- Acronym / sponsor ID
- 2023-FXY-173-Department of CRC
- Conditions
- Colorectal Cancer
- Keywords
- Colorectal cancer, Neoadjuvant chemoradiotherapy, Neoadjuvant immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 53 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Nov 2023 (estimated)
- Primary completion
- 1 Sep 2024 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 25 Oct 2023 (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.
For locally advanced rectal cancer, the initial goal of neoadjuvant chemoradiotherapy is to reduce local recurrence, but the pathologic complete response (PCR) rate is low, and distant metastasis becomes the main treatment failure pattern. With the gradual optimization of neoadjuvant chemotherapy regimens, the tumor regression efficacy in patients has improved, leading to increased organ preservation and reduced distant metastasis. Therefore, neoadjuvant treatment for locally advanced rectal cancer has transitioned from an era focused on local control of recurrence to an era focused on improving tumor regression, organ preservation, and long-term survival. Thus, there is a trend towards intensifying the whole course of neoadjuvant treatment for rectal cancer to preserve organ function. The combination of chemotherapy, immunotherapy, and radiotherapy is currently the most powerful approach to maximize tumor regression and achieve organ preservation in low rectal cancer. Currently, several clinical studies on the use of PD-1 inhibitors in combination with preoperative chemoradiotherapy for locally advanced rectal cancer are ongoing internationally, with the majority focusing on PD-1 monotherapy or PD-1 combined with the CapOX regimen in combination with synchronous chemoradiotherapy as neoadjuvant treatment. However, there is no specific research reported on the use of PD-1 combined with FOLFOXIRI regimen in combination with synchronous chemoradiotherapy as a whole course neoadjuvant treatment for pMMR (proficient mismatch repair) locally advanced rectal cancer. Based on the above evidence from evidence-based medicine, we plan to conduct a phase II prospective clinical study to explore the efficacy and treatment safety of PD-1 monoclonal antibody and FOLFOXIRI chemotherapy combined with intensity-modulated radiotherapy as a whole course neoadjuvant treatment in pMMR locally advanced low rectal cancer. The results of this study may open up new treatment approaches for optimizing whole course neoadjuvant chemotherapy in locally advanced rectal cancer and provide a novel treatment strategy for organ preservation in pMMR rectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Serplulimab+FOLFOXIRI | Experimental | Drug: Serplulimab + FOLFOXIRI, Radiation: Radiation therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- The pathological confirmation is rectal adenocarcinoma. Additionally, the tumor biopsy immunohistochemistry indicates pMMR, with all MSH1, MSH2, MSH6, and PMS2 showing positive expression.
- Age: 18 to 75 years old,allgenders
- MRI examination confirms that the lower margin of the tumor is within 5cm from the anal verge.
- Clinical stage cT3-4N0M0 or cTxN+M0, with or without positive MRF, with or without positive EMVI, estimated to be eligible for R0 resection.
- No signs of intestinal obstruction before surgery; or resolution of obstruction after proximal colostomy surgery
Key exclusion criteria (8 listed)
- Co-existing with other serious illnesses, including severe electrolyte disorders, bleeding tendencies, etc.
- Active or uncontrolled severe infections: a) Known human immunodeficiency virus (HIV) infection. b) Known clinically significant liver disease history, including viral hepatitis [known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (>1×104 copies/mL or >2000 IU/mL)]. c) Known hepatitis C virus (HCV) infection with positive HCV RNA (>1×103 copies/mL), or other hepatitis, liver cirrhosis.
- Women who are pregnant or breastfeeding and have childbearing potential but are not taking adequate contraceptive measures.
- Patients with severe brain disorders or mental illnesses (such as depression, mania, obsessive-compulsive disorder, and schizophrenia) that affect the patient's ability to self-report.
- Patients with autoimmune diseases, blood system disorders, and a history of organ transplantation, long-term use of steroids, or immunosuppressive agents
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 |
|---|---|---|
| Serplulimab + FOLFOXIRIStarting from day 0, the patient will receive 8 cycles of FOLFOXIRI regimen at specific intervals. The FOLFOXIRI regimen includes irinotecan 165mg/m2, oxaliplatin 85mg/m2, calcium folinate 200mg/m2 on day 1, followed by continuous intravenous infusion of 5-FU 2400mg/m2/day for 46 hours. This regimen is repeated every 14 days.During radiotherapy (Monday to Friday), the patient will receive capecitabine 1650mg/m2/day orally twice daily. Serplulimab immunotherapy will be administered every 2 weeks during the FOLFOXIRI neoadjuvant chemotherapy period. Serplulimab will be given on the first day and the 14th day of radiotherapy, dissolved in 100ml normal saline and administered intravenously over 30-60 minutes at a dose of 200mg. | Drug | Serplulimab+FOLFOXIRI |
| Radiation therapyRadiation therapy | Radiation | Serplulimab+FOLFOXIRI |
Primary outcome
Complete tumor response rate.
Time frame: Immediately After obtaining the surgical specimen.
Including pathological complete response (pCR) and clinical complete response (cCR); pathological complete response is defined as the absence of visible tumor cells in the rectal specimen obtained during surgery
1 secondary outcome
Sphincter preservation rate
Time frame: During 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 25 Oct 2023.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Serplulimab + FOLFOXIRI and Radiation therapy in people with Colorectal Cancer, run by Sun Yat-sen University.
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 11 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: opening soon, as of the sponsor's last update on 25 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Junzhong Lin, Prof (020-87343533, linjzh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete tumor response rate. (time frame: Immediately After obtaining the surgical specimen.). 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 25 Oct 2023.