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NCT Number: 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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Locally Advanced Rectal Cancer (LARC)

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200092, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.
  • 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.

Treatment and study plan

neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor therapy

Drug

Preoperative treatment with 4-6 cycles of mFOLFOX6 regimen combined with serplulimab

Primary outcomes

  1. Pathological complete response

    Time frame: Day 7 after surgery

  2. Major Pathological Response

    Time frame: Day 7 after surgery

Secondary outcomes

  1. Tumor regression grade

    Time frame: Day 7 after surgery

  2. Radiologic Response

    Time frame: Preoperative evaluation

  3. Neoadjuvant rectal score

    Time frame: Day 7 after surgery

    The Neoadjuvant rectal score ranges from 0 to 100, with higher scores indicating poorer response to neoadjuvant therapy.

  4. Postoperative complication

    Time frame: Within 2 weeks post-surgery

  5. Disease free survival

    Time frame: Three years after surgery

  6. Relapse free survival

    Time frame: Three years after surgery

  7. Wexner fecal incontinence scale

    Time frame: evaluated every 3 months for 3 years after surgery

    Utilized to evaluate anal function, with higher scores indicating poorer anal function.

  8. overall survival

    Time frame: Three years after surgery

  9. 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.

Sponsors and collaborators

Lead sponsor

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Other

Registry information

Official study 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)

Acronym: FIRM

Important dates

Study start
2024
Primary completion
2025
Study completion
2027
First posted
Nov 14, 2024
Registry last updated
Jan 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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