Clinical trial NCT06688786: 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
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Locally Advanced Rectal Cancer (LARC)
Keywords: rectcal cancer
microsatellite stable
FOLFOX
neoadjuvant chemotherapy
PD-1 antibodies
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2024-11-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

1. Advanced (cT3-4NxM0 or cTxN+M0) rectal cancer with the lower tumor margin within 15 cm of the anal verge
2. Histopathology confirmed adenocarcinoma with an pMMR/MSS genetic profile.
3. Absence of bowel obstruction, or bowel obstruction relieved by proximal colostomy.
4. Age: 18-75
5. ECOG: 0-1
6. No prior chemotherapy, radiotherapy, targeted therapy, or immunotherapy received.
7. Female participants must be non-lactating, with a negative pregnancy test result.

Exclusion Criteria:

1. Patients with distant metastasis
2. History of receiving chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
3. Active autoimmune disease requiring systemic treatment within the 2 years prior to enrollment.
4. History of other malignancies within the past 5 years, excluding cured cervical carcinoma in situ or basal cell carcinoma of the skin.
5. History of HIV infection, or active chronic hepatitis B or C with high viral DNA copy numbers.
6. Patients with active tuberculosis currently receiving anti-tuberculosis treatment or treated with anti-tuberculosis therapy within the past year prior to screening.
7. Known or suspected allergy to the study drug or any study-related medications administered.
8. Presence of severe cardiovascular or cerebrovascular disease.
9. 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.
10. Receiving systemic corticosteroid treatment or other immunosuppressive agents within 14 days prior to the first dose, or immunostimulants within 4 weeks.
11. History of confirmed neurological or psychiatric disorders, including epilepsy or dementia.
12. The participant may be unable to complete the study due to other reasons, or the investigator considers them unsuitable for inclusion.
13. Refusal to sign the informed consent form.

Primary outcomes:
measure: Major Pathological Response
timeFrame: Day 7 after surgery
Secondary outcomes:
measure: Pathological complete response rate
timeFrame: Day 7 after surgery
measure: Tumor regression grade
timeFrame: Day 7 after surgery
measure: Radiologic Response Ratio
timeFrame: Preoperative evaluation
measure: Postoperative complication rate
timeFrame: Within 2 weeks post-surgery
measure: Disease free survival
timeFrame: Three years after surgery
measure: Relapse free survival
timeFrame: Three years after surgery
measure: Wexner fecal incontinence scale
timeFrame: evaluated every 3 months for 3 years after surgery
measure: overall survival
timeFrame: Three years after surgery
measure: Adverse events
timeFrame: 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.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
References: