PD-1 + FOLFOXIRI vs CAPOX as Total Neoadjuvant Therapy for pMMR Low Rectal Cancer

Summary

The goal of this clinical trial is to find out if adding a PD-1 antibody (serplulimab) to FOLFOXIRI chemotherapy and radiotherapy works better than CAPOX chemotherapy with radiotherapy as total neoadjuvant therapy for adults with pMMR locally advanced low rectal cancer. It will also look at the safety of these treatments and how they affect long-term outcomes such as organ preservation and survival.

The main questions it aims to answer are:

Does PD-1 antibody plus FOLFOXIRI with radiotherapy improve 3-year event-free survival compared with CAPOX with radiotherapy?

Does this treatment increase the chance of clinical complete response and avoiding a permanent stoma (sphincter-preserving or non-surgical "watch-and-wait" management)?

What side effects and medical problems occur during and after these treatments?

Researchers will compare:

Group A (experimental group): PD-1 antibody (serplulimab) plus FOLFOXIRI chemotherapy combined with long-course radiotherapy as total neoadjuvant therapy.

Group B (control group): CAPOX chemotherapy combined with long-course radiotherapy as total neoadjuvant therapy.

Participants will:

Sign an informed consent form and have screening tests (physical exam, blood tests, ECG, imaging such as MRI/CT, endoscopy) to confirm they can join the trial.

Be randomly assigned (like drawing lots) to Group A or Group B. Receive several cycles of chemotherapy together with a 5-week course of pelvic radiotherapy before surgery; the experimental group will also receive PD-1 antibody during part of the chemotherapy and radiotherapy period.

Have regular clinic visits for checkups, blood tests, and assessment of side effects during treatment.

After neoadjuvant therapy, have MRI/CT and endoscopy to assess tumor response. Depending on the response, they may:

Receive surgery to remove the rectal tumor, or

If a clinical complete response is achieved and both doctor and patient agree, enter a "watch-and-wait" program instead of immediate surgery.

Provide blood samples and allow tumor tissue to be collected (for example, from biopsy and surgery) for future research (such as building PDX models and testing blood markers).

Be followed regularly for at least 5 years with clinic visits, blood tests (including CEA), imaging, and colonoscopy to check for tumor recurrence, side effects, and quality of life.

Conditions

• Locally Advanced Low Rectal Adenocarcinoma
• pMMR (Microsatellite Stable Rectal Cancer)

Interventions

DRUG

Serplulimab

Serplulimab will be administered intravenously in combination with FOLFOXIRI chemotherapy and long-course pelvic radiotherapy as part of total neoadjuvant therapy in the experimental arm.

DRUG

FOLFOXIRI chemotherapy

The FOLFOXIRI chemotherapy regimen (5-fluorouracil, leucovorin, oxaliplatin, irinotecan) will be administered according to the study protocol as part of total neoadjuvant therapy in the experimental arm, in combination with serplulimab and long-course pelvic radiotherapy.

DRUG

CAPOX chemotherapy

The CAPOX chemotherapy regimen (capecitabine plus oxaliplatin) will be administered according to the study protocol as part of total neoadjuvant therapy in the active comparator arm, in combination with long-course pelvic radiotherapy.

RADIATION

Long-course pelvic radiotherapy

Long-course pelvic external beam radiotherapy will be delivered according to institutional standards as part of total neoadjuvant therapy in both study arms, in combination with chemotherapy (FOLFOXIRI plus serplulimab in the experimental arm or CAPOX in the active comparator arm).

Sponsors & Collaborators

• Sun Yat-sen University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-12-29

Primary Completion

2028-12-29

Completion

2028-12-29

Countries

• China

Study Locations