Neoadjuvant therapy for synchronous multiple primary colorectal cancer

Safety and Efficacy of PD-1 Monoclonal Antibody With or Without mFOLFOX6 Neoadjuvant Therapy in Patients With Local Advanced Deficient Mismatch Repair/Microsatellite Instability-high Synchronous Multiple Primary Colorectal Cancer (sMPCC)

This study is testing a new combination of immunotherapy and chemotherapy to see if it helps people with multiple primary colorectal cancer feel better and have better outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 17 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06002789 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of combining PD-1 monoclonal antibody with mFOLFOX6 as a neoadjuvant therapy for patients with synchronous multiple primary colorectal cancer (sMPCC). The study focuses on patients with different microsatellite instability (MSI) statuses, specifically those with dMMR/MSI-H tumors. Participants will undergo comprehensive staging and assessment to determine eligibility, and the treatment aims to improve outcomes for this rare cancer type. The trial is designed to provide insights into the effectiveness of immunotherapy in conjunction with standard chemotherapy for sMPCC patients.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed synchronous multiple primary colorectal cancer and specific MSI statuses.

Not a fit: Patients with single primary colorectal cancer or those without the required MSI status may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the outcomes for patients with synchronous multiple primary colorectal cancer.

How similar studies have performed: Other studies have shown promising results with PD-1 monoclonal antibody therapies in colorectal cancer, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Histological confirmation of simultaneous multiple primary colorectal cancer (sMPCC);
2. 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;
3. Clinical staging T3-4NxM0, with or without positive MRF, with or without positive EMVI;
4. 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;
5. No intestinal obstruction symptom，or obstruction relieved after proximal colostomy;
6. No colorectal surgery history;
7. No chemotherapy or radiotherapy history;
8. 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;
9. No endocrinotherapy history restriction;
10. informed consent assigned.

Exclusion Criteria:

1. 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;
2. Severe hypertension not well controlled by drugs;
3. HIV infection history or active phase of chronic Hepatitis B or C(high copies of virus DNA);
4. Active tuberculosis(TB), accepting anti-TB treatment or anti-TB treatment within 1 year before trial screen;
5. Other active clinical severe infection(NCI-CTC AE V5.0);
6. Outside pelvic distant metastasis evidences;
7. Dyscrasia, organ dysfunction;
8. Pelvic or abdominal radiotherapy history;
9. Epilepsy need treatments(Steroid or anti-epilepsy therapy);
10. Other malignant tumor history within 5 years;
11. Over abuse of drugs, medical and psychological or social conditions that might interfere patients or evaluation of the study results;
12. Any active autoimmune disease or autoimmune disease history (including but not restricted: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism, asthma need bronchodilators);
13. Any anti-infection vaccine injection 4 weeks before inclusion;
14. Long-term exposure to immune-suppressor, combination of systemic or topical use of corticosteroids (dose\>10mg/day prednisolone or equivalent hormone);
15. Known or suspicious allergy to any study related drugs;
16. Any unstable state might cause damage to the safety and compliance of patients;
17. Pregnant or breast feeding women who has ability to have children while without contraception;
18. Refuse to sign informed consent.

Where this trial is running

Guangzhou, Guangdong

• The Sixth Affiliated Hospital, Sun Yatsen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Jun Huang, MD

Conditions Multiple Cancer; Colorectal Cancer; Synchronous multiple primary colorectal cancer; PD-1; Neoadjuvant treatment; MSI-H