Safety and Efficacy of PD-1 ± mFOLFOX6 Neoadjuvant Therapy in Local Advanced sMPCC

NCT06002789 | Recruiting Phase 2

• 1 other identifier: E2023073
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

At present, radical resection ± preoperative neoadjuvant chemotherapy for colorectal cancer is still the standard comprehensive treatment. In recent years, immunotherapy of PD-1 monoclonal antibody has a significant effect in the second-line/first-line treatment of dMMR/MSI-H advanced colorectal cancer and the neoadjuvant treatment of early colorectal cancer. Synchronous multiple primary colorectal cancer (sMPCC) is a relatively rare type of colorectal cancer (CRC) that refers to the simultaneous occurrence of 2 or more independent primary malignancies in the colon or rectum. The recent large-scale, single-center retrospective study of the investigator showed that compared with single primary colorectal cancer (SPCRC)patients, the incidence of dMMR/MSI-H was significantly higher in sMPCC patients. Besides, a certain proportion of sMPCC patients could both have MSI and MSS tumors at the same time. There is no standard regimen for this patients so far. This study intends to treat the MSI-H/MSS (dMMR/pMMR) mixed sMPCC patients with combination of mFOLFOX6+PD-1 monoclonal antibody neoadjuvant therapy, and treat the all-MSI-H (dMMR) sMPCC patients with single-drug PD-1 monoclonal antibody neoadjuvant therapy. Given the current gaps in the guideline, the investigator intends to take the lead in carrying out this open, multi-center, prospective clinical phase II study. This study might provide a clinical evidence for individual treatment of sMPCC patients, in preserving the functions and organs to the greatest extent.

Conditions

Colorectal Cancer; Multiple Cancer

Keywords

Synchronous multiple primary colorectal cancer; PD-1; Neoadjuvant treatment; MSI-H

Outcome Measures

Primary Outcomes (1)

• pCR rate

  pathological complete remission rate

  1 year

Secondary Outcomes (6)

• Incidence rate of Grade ≥3 PD-1monoclonal antibody-related adverse events

  1 year

• Incidence rate of Grade ≥3 chemotherapy-related adverse events

  1 year

• R0 resection rate

  1 year

• Down-stage rate

  1 year

• 3 years DFS Rate

  3 years

Study Arms (1)

MSI-H/MSS (dMMR/pMMR) mixed sMPCC or all-MSI-H (dMMR) sMPCC

EXPERIMENTAL

1. MSI-H/MSS (dMMR/pMMR) mixed sMPCC: Synchronous multiple primary colorectal cancer consist of MSI/dMMR and MSS/pMMR tumors at the same time 2. all-MSI-H (dMMR) sMPCC: Synchronous multiple primary colorectal cancer with all MSI/dMMR tumors

Drug: MSI-H/MSS (dMMR/pMMR) mixed sMPCC: combination of mFOLFOX6+PD-1 monoclonal antibody neoadjuvant therapy; Drug: All-MSI-H (dMMR) sMPCC: single-drug PD-1 monoclonal antibody neoadjuvant therapy

Interventions

MSI-H/MSS (dMMR/pMMR) mixed sMPCC: combination of mFOLFOX6+PD-1 monoclonal antibody neoadjuvant therapy DRUG

For MSI-H/MSS (dMMR/pMMR) mixed sMPCC, a combination of neoadjuvant chemotherapy with mFOLFOX6 and immunotherapy with PD-1 monoclonal antibody are applied.

Also known as: Mixed sMPCC

MSI-H/MSS (dMMR/pMMR) mixed sMPCC or all-MSI-H (dMMR) sMPCC

All-MSI-H (dMMR) sMPCC: single-drug PD-1 monoclonal antibody neoadjuvant therapy DRUG

For all-MSI-H (dMMR) sMPCC, single-drug PD-1 monoclonal antibody immunotherapy is applied.

Also known as: MSI-H sMPCC

MSI-H/MSS (dMMR/pMMR) mixed sMPCC or all-MSI-H (dMMR) sMPCC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of simultaneous multiple primary colorectal cancer (sMPCC);
• Tumor biopsy immunohistochemistry of at least one tumor lesion identified dMMR, including the expression loss of one or more of the four proteins MSH1, MSH2, MSH6 and PMS2; or at least one tumor lesion identified MSI-H by polymerase chain reaction or next-generation sequencing technique;
• Clinical staging T3-4NxM0, with or without positive MRF, with or without positive EMVI;
• Staging method: all patients undergo chest,abdominal and pelvic enhanced CT, rectal palpation, high resolution MRI examination，positive perienteric lymph node(LN): short diameter ≥10mm LN or LN with typical metastatic shape and MRI character, clinical data should be re-evaluated and judged by center evaluation group when there are contradictory stagings，distant metastasis were excluded by chest and abdominal enhanced CT and pelvic enhanced MRI;
• No intestinal obstruction symptom，or obstruction relieved after proximal colostomy;
• No colorectal surgery history;
• No chemotherapy or radiotherapy history;
• No biopharmaceutical treatment history(such as monoclonal antibody), immunotherapy(such as anti PD-1antibody, anti PD-L1 antibody, anti PD-L2 antibody or anti CTLA-4), or other research drug treatment;
• No endocrinotherapy history restriction;
• informed consent assigned.

You may not qualify if:

• Arrhythmia need anti-arrhythmia treatment(except β-blocking agent or Digoxin), symptomatic coronary heart disease or myocardial ischemia(myocardial infarction within 6 months) or congestive heart-failure (CHF) \> NYHA grade II;
• Severe hypertension not well controlled by drugs;
• HIV infection history or active phase of chronic Hepatitis B or C(high copies of virus DNA);
• Active tuberculosis(TB), accepting anti-TB treatment or anti-TB treatment within 1 year before trial screen;
• Other active clinical severe infection(NCI-CTC AE V5.0);
• Outside pelvic distant metastasis evidences;
• Dyscrasia, organ dysfunction;
• Pelvic or abdominal radiotherapy history;
• Epilepsy need treatments(Steroid or anti-epilepsy therapy);
• Other malignant tumor history within 5 years;
• Over abuse of drugs, medical and psychological or social conditions that might interfere patients or evaluation of the study results;
• Any active autoimmune disease or autoimmune disease history (including but not restricted: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism, asthma need bronchodilators);
• Long-term exposure to immune-suppressor, combination of systemic or topical use of corticosteroids (dose\>10mg/day prednisolone or equivalent hormone);
• Known or suspicious allergy to any study related drugs;
• Any unstable state might cause damage to the safety and compliance of patients;

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital, Sun Yatsen University

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Jun Huang, MD

CONTACT

13926451242; huangj97@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: MSI-H/MSS (dMMR/pMMR) mixed sMPCC or all-MSI-H (dMMR) sMPCC

Study Record Dates

• First Submitted: August 16, 2023
• First Posted: August 21, 2023
• Study Start: May 1, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 27, 2026

Record last verified: 2026-02

Locations

CN (1)