Locally Advanced Rectal Cancer (LARC)FIRMNCT06688786
A Pospective, Single-arm, Multicenter Clinical Trial Evaluating Preoperative Neoadjuvant mFOLFOX6 Chemotherapy in Combination With PD1 Monoclonal Antibody in MSS/pMMR Locally Advanced Rectal Cancer
A study testing neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapy in people with Locally Advanced Rectal Cancer (LARC), run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
Preoperative neoadjuvant chemoradiotherapy can induce tumor regression and reduce the risk of postoperative recurrence, serving as the standard treatment for locally advanced rectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Locally Advanced Rectal Cancer (LARC)
- What is being tested?
- neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2024to 31 Dec 2027
- Phase
- Interventional
- 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
- Advanced (cT3-4NxM0 or cTxN+M0) rectal cancer with the lower tumor margin within 15 cm of the anal verge
- Histopathology confirmed adenocarcinoma with an pMMR/MSS genetic profile.
- Absence of bowel obstruction, or bowel obstruction relieved by proximal colostomy.
- Age: 18-75
- ECOG: 0-1
- No prior chemotherapy, radiotherapy, targeted therapy, or immunotherapy received.
- Female participants must be non-lactating, with a negative pregnancy test result.
Who cannot join
- Patients with distant metastasis
- History of receiving chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
- Active autoimmune disease requiring systemic treatment within the 2 years prior to enrollment.
- History of other malignancies within the past 5 years, excluding cured cervical carcinoma in situ or basal cell carcinoma of the skin.
- History of HIV infection, or active chronic hepatitis B or C with high viral DNA copy numbers.
- Patients with active tuberculosis currently receiving anti-tuberculosis treatment or treated with anti-tuberculosis therapy within the past year prior to screening.
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- Known or suspected allergy to the study drug or any study-related medications administered.
- Presence of severe cardiovascular or cerebrovascular disease.
- Within 14 days prior to the first dose, presence of a severe active or uncontrolled infection requiring systemic therapy, or unexplained fever >38.5°C.
- Receiving systemic corticosteroid treatment or other immunosuppressive agents within 14 days prior to the first dose, or immunostimulants within 4 weeks.
- History of confirmed neurological or psychiatric disorders, including epilepsy or dementia.
- The participant may be unable to complete the study due to other reasons, or the investigator considers them unsuitable for inclusion.
- Refusal to sign the informed consent form.
Trial locations and contacts
1 site in 1 country.
China1 site
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200092
About this study
Official title: A Pospective, Single-arm, Multicenter Clinical Trial Evaluating Preoperative Neoadjuvant mFOLFOX6 Chemotherapy in Combination With PD1 Monoclonal Antibody in MSS/pMMR Locally Advanced Rectal Cancer (FIRM Study)
Preoperative neoadjuvant chemoradiotherapy can induce tumor regression and reduce the risk of postoperative recurrence, serving as the standard treatment for locally advanced rectal cancer. However, neoadjuvant radiotherapy may increase the risk of postoperative complications, proctitis, enteritis, and reduced anal function. Exploring radiation-free approaches to prevent the effects of radiotherapy toxicity on postoperative complications and quality of life is now a significant research focus. Neoadjuvant chemotherapy represents a promising approach in the neoadjuvant treatment of rectal cancer. Neoadjuvant chemotherapy avoids the impact of radiotherapy on organ function, reduces the incidence of postoperative anastomotic leakage, and is beneficial for long-term anal function preservation. However, its low tumor regression rate limits its application in the neoadjuvant treatment of rectal cancer. For patients with locally advanced rectal cancer, there is an urgent need for a new neoadjuvant treatment strategy that can both significantly improve tumor regression rates and reduce the risk of postoperative anastomotic leakage, and protect long-term anal function. PD-1 inhibitors are highly effective in treating microsatellite instability-high (MSI-H) colorectal cancer patients, but show poor efficacy in the 95% of patients with microsatellite stable (MSS) tumors. The challenge now is to find combination therapies that can convert tumors into an "immune-activated tumor," thereby enhancing the effectiveness of immunotherapy in MSS patients. Oxaliplatin and 5-fluorouracil have roles in releasing tumor antigen epitopes, activating CD8+ cells, and reshaping the immune microenvironment. Multiple clinical studies and animal experiments have shown that combining PD-1 antibodies with FOLFOX generates a synergistic effect, showing strong antitumor activity. This study evaluates the efficacy, safety, and impact on postoperative anal function of preoperative neoadjuvant treatment with FOLFOX chemotherapy combined with PD-1 inhibitors in patients with MSS-type advanced rectal cancer. The radiotherapy-free approach aims to avoid radiotherapy-related toxicity, offering significant potential to enhance the efficacy of neoadjuvant chemotherapy, improve long-term survival, and protect anal function.
- Conditions
- Locally Advanced Rectal Cancer (LARC)
- Being tested
- neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapy
- Keywords
- rectcal cancer, microsatellite stable, FOLFOX, neoadjuvant chemotherapy, PD-1 antibodies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapyDrug
Preoperative treatment with 4-6 cycles of mFOLFOX6 regimen combined with serplulimab
| Study group | Role | What they receive |
|---|---|---|
| Combinational treatment group | Experimental | neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapy Receives: Drug: neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response
Measured: Day 7 after surgery
Major Pathological Response
Measured: Day 7 after surgery
Secondary outcomes (9)
Tumor regression grade
Measured: Day 7 after surgery
Radiologic Response
Measured: Preoperative evaluation
Neoadjuvant rectal score
The Neoadjuvant rectal score ranges from 0 to 100, with higher scores indicating poorer response to neoadjuvant therapy.
Measured: Day 7 after surgery
Postoperative complication
Measured: Within 2 weeks post-surgery
Disease free survival
Measured: Three years after surgery
Relapse free survival
Measured: Three years after surgery
Wexner fecal incontinence scale
Utilized to evaluate anal function, with higher scores indicating poorer anal function.
Measured: evaluated every 3 months for 3 years after surgery
overall survival
Measured: Three years after surgery
Adverse events
Measured: Prior to surgery, adverse events are evaluated the day before each chemotherapy cycle. After surgery, adverse events are evaluated at months 3, 6, 9, and 12.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2024
- Study start1 Nov 2024
- Primary completion31 Jul 2025
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Rectal Cancer (LARC)Studies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tingyu Wu, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06688786
- Sponsor's protocol ID
- XHEC-C-2024-179-2
- Acronym
- FIRM
- Status last verified
- Jan 2026
- First submitted
- 8 Nov 2024
- Last updated
- 27 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: In this study personal information and data such as patient history, physical examination results, surgical records, and study questionnaire data will be collected. These data will be used to evaluate the efficacy and safety of the therapeutic regimen and for academic publication. The researcher will treat the personal data of patients confidentially and anonymize the data and information in any public release of the results of the study.
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pospective, Single-arm, Multicenter Clinical Trial Evaluating Preoperative Neoadjuvant mFOLFOX6 Chemotherapy in Combination With PD1 Monoclonal Antibody in MSS/pMMR Locally Advanced Rectal Cancer (FIRM Study)
- ClinicalTrials.gov ID
- NCT06688786
- Acronym / sponsor ID
- FIRM / XHEC-C-2024-179-2
- Conditions
- Locally Advanced Rectal Cancer (LARC)
- Keywords
- rectcal cancer, microsatellite stable, FOLFOX, neoadjuvant chemotherapy, PD-1 antibodies
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Xinhua Hospital, Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 31 Jul 2025 (actual)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 14 Nov 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.
Preoperative neoadjuvant chemoradiotherapy can induce tumor regression and reduce the risk of postoperative recurrence, serving as the standard treatment for locally advanced rectal cancer. However, neoadjuvant radiotherapy may increase the risk of postoperative complications, proctitis, enteritis, and reduced anal function. Exploring radiation-free approaches to prevent the effects of radiotherapy toxicity on postoperative complications and quality of life is now a significant research focus. Neoadjuvant chemotherapy represents a promising approach in the neoadjuvant treatment of rectal cancer. Neoadjuvant chemotherapy avoids the impact of radiotherapy on organ function, reduces the incidence of postoperative anastomotic leakage, and is beneficial for long-term anal function preservation. However, its low tumor regression rate limits its application in the neoadjuvant treatment of rectal cancer. For patients with locally advanced rectal cancer, there is an urgent need for a new neoadjuvant treatment strategy that can both significantly improve tumor regression rates and reduce the risk of postoperative anastomotic leakage, and protect long-term anal function. PD-1 inhibitors are highly effective in treating microsatellite instability-high (MSI-H) colorectal cancer patients, but show poor efficacy in the 95% of patients with microsatellite stable (MSS) tumors. The challenge now is to find combination therapies that can convert tumors into an "immune-activated tumor," thereby enhancing the effectiveness of immunotherapy in MSS patients. Oxaliplatin and 5-fluorouracil have roles in releasing tumor antigen epitopes, activating CD8+ cells, and reshaping the immune microenvironment. Multiple clinical studies and animal experiments have shown that combining PD-1 antibodies with FOLFOX generates a synergistic effect, showing strong antitumor activity. This study evaluates the efficacy, safety, and impact on postoperative anal function of preoperative neoadjuvant treatment with FOLFOX chemotherapy combined with PD-1 inhibitors in patients with MSS-type advanced rectal cancer. The radiotherapy-free approach aims to avoid radiotherapy-related toxicity, offering significant potential to enhance the efficacy of neoadjuvant chemotherapy, improve long-term survival, and protect anal function.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combinational treatment group | Experimental | Drug: neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapyneoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Advanced (cT3-4NxM0 or cTxN+M0) rectal cancer with the lower tumor margin within 15 cm of the anal verge
- Histopathology confirmed adenocarcinoma with an pMMR/MSS genetic profile.
- Absence of bowel obstruction, or bowel obstruction relieved by proximal colostomy.
- Age: 18-75
- ECOG: 0-1
Key exclusion criteria (13 listed)
- Patients with distant metastasis
- History of receiving chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
- Active autoimmune disease requiring systemic treatment within the 2 years prior to enrollment.
- History of other malignancies within the past 5 years, excluding cured cervical carcinoma in situ or basal cell carcinoma of the skin.
- History of HIV infection, or active chronic hepatitis B or C with high viral DNA copy numbers.
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 mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapyPreoperative treatment with 4-6 cycles of mFOLFOX6 regimen combined with serplulimab | Drug | Combinational treatment group |
Primary outcome
Pathological complete response
Time frame: Day 7 after surgery
Major Pathological Response
Time frame: Day 7 after surgery
9 secondary outcomes
Tumor regression grade
Time frame: Day 7 after surgery
Radiologic Response
Time frame: Preoperative evaluation
Neoadjuvant rectal score
Time frame: Day 7 after surgery
Postoperative complication
Time frame: Within 2 weeks post-surgery
Disease free survival
Time frame: Three years after surgery
Relapse free survival
Time frame: Three years after surgery
Wexner fecal incontinence scale
Time frame: evaluated every 3 months for 3 years after surgery
overall survival
Time frame: Three years after surgery
Adverse events
Time frame: Prior to surgery, adverse events are evaluated the day before each chemotherapy cycle. After surgery, adverse events are evaluated at months 3, 6, 9, and 12.
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 27 Jan 2026.
- Individual participant dataSharing planned: Yes. In this study personal information and data such as patient history, physical examination results, surgical records, and study questionnaire data will be collected. These data will be used to evaluate the efficacy and safety of the therapeutic regimen and for academic publication. The researcher will treat the personal data of patients confidentially and anonymize the data and information in any public release of the results of the study.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapy in people with Locally Advanced Rectal Cancer (LARC), run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine 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 13 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: under way, not looking for participants, as of the sponsor's last update on 27 Jan 2026. 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?
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response (time frame: Day 7 after surgery). 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?
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 27 Jan 2026.