Neoadjuvant treatment for locally advanced colorectal cancer using mFOLFOXIRI and Cadonilimab

Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 Alone in Locally Advanced Colorectal Cancer: a Randomized Control Phase II Study (OPTICAL-2)

This study is testing a new combination of chemotherapy and an immune treatment to see if it helps people with locally advanced colorectal cancer do better before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 143 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: immunotherapy, prednisone, nivolumab, ipilimumab, Cadonilimab, chemotherapy, fruquintinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05571644 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of neoadjuvant treatment combining mFOLFOXIRI with Cadonilimab (AK104) compared to mFOLFOX6 in patients with locally advanced colorectal cancer. It is a phase II, prospective, randomized trial that includes patients with specific tumor characteristics and aims to assess treatment response after 6 cycles of chemotherapy before surgery. The study also incorporates imaging evaluations to determine tumor regression and feasibility for surgical resection. The goal is to improve survival outcomes by exploring new treatment combinations.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with locally advanced colorectal adenocarcinoma who have not received prior systemic antitumor therapy.

Not a fit: Patients with distant metastasis or those who have previously undergone systemic antitumor therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could enhance survival rates and improve outcomes for patients with locally advanced colorectal cancer.

How similar studies have performed: Previous studies have shown promising results with neoadjuvant therapies in colorectal cancer, but the specific combination being tested here is novel.

Eligibility criteria

Inclusion Criteria:

1. Aged 18-70;
2. Colorectal adenocarcinoma with definite histological evidence;
3. ECOG Performance status score is 0-1
4. Colon cancer was evaluated as T3\>5mm or T4 by contrast-enhanced CT examination of the chest, abdomen and pelvis, and distant displacement was excluded; Rectal cancer was graded as T3-4 and/or N+ by pelvic contrast-enhanced MRI examination, and the lower margin of the tumor was less than 12cm away from the anal margin. Distant metastasis was excluded by chest, abdomen and pelvis CT.
5. The primary rectal tumor was assessed as complete resections by a multidisciplinary collaboration group on colorectal cancer, including at least 2 gastrointestinal surgeons and 1 radiologist;
6. No previous systemic antitumor therapy for colorectal cancer, including cytotoxic drugs, immunotherapy, molecular targeted therapy, etc.;
7. Adequate organ function based on the following laboratory test values obtained within 7 days prior to treatment:

   Hemoglobin ≥90g/L, neutrophil count ≥1.5×109/L, platelet count ≥75×109/L, serum total bilirubin ≤1.5× upper limit of normal value (UNL), aspartate transferase ≤2×UNL, alanine transferase ≤3×UNL, serum creatinine ≤1.5×UNL;
8. Willing and able to comply with research protocols and visit plans.

Exclusion Criteria:

1. The patient was complicated with obstruction, active bleeding, or perforation and required emergency surgery or stent placement;
2. Active, known or suspected autoimmune diseases (except type I diabetes, residual hypothyroidism requiring only hormone replacement due to autoimmune conditions, or autoimmune diseases that are not expected to recur in the absence of external triggers);
3. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml; Hepatitis C, defined as HCV-RNA above the detection limit of the assay) or co-infection with hepatitis B and C;
4. Known allergy to the treatment drug or allergy or intolerance to its ingredients;
5. Major surgery or severe trauma, such as laparotomy, thoracotomy, laparoscopic organ resection, etc. within the previous 4 weeks (the surgical incision should be completely healed before enrollment);
6. Existing or coexisting other active malignancies (except those that have been treated with curative therapy and remain disease-free for more than 5 years or carcinoma in situ that can be cured by adequate treatment);
7. Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody and anti-cytotoxic T-lymphocyte-associated protein 4 (Cytotoxic T-lymphocyte-associated protein 4) antibody. Ctla-4) antibodies or other drugs/antibodies that act on T-cell costimulatory or checkpoint pathways;
8. Had active coronary artery disease, severe/unstable angina pectoris or newly diagnosed angina pectoris or myocardial infarction within 6 months prior to study enrollment; Thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, deep vein thrombosis, occurred within the previous 6 months;
9. The New York Heart Association (NYHA) class II or higher congestive Heart failure (see Appendix 3);
10. Presence of active inflammatory bowel disease or other colorectal disease leading to chronic diarrhea;
11. The presence of any toxicity (Common Terminology Criteria for Adverse Events, CTCAE) (version 5.0) grade 1 or above (except anemia, alopecia, and skin pigmentation) caused by previous treatment that has not subsided;
12. Previous or current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe impairment of pulmonary function and other lung diseases;
13. Active tuberculosis (TB), receiving anti-TB therapy or receiving anti-TB therapy within 1 year before the first dose;
14. Persons with known syphilis infection requiring treatment;
15. Had used immunosuppressive drugs within 4 weeks before the first dose, Does not include the nasal spray, inhalation, or other ways of topical corticosteroids or physiological doses of systemic corticosteroids (i.e., no more than 10 mg/day prednisone or other equivalent dose glucocorticoids), allows for prevention of allergic reactions, or treatment of diseases such as asthma, chronic obstructive pulmonary disease of breathing difficulties for the temporary use of glucocorticoid;
16. Receive live attenuated vaccine within 4 weeks before the first dose or during the study period;
17. Pregnant or lactating women; Women of reproductive age (\< 2 years after last menstruation) who do not use or refuse to use effective non-hormonal contraception or men at risk of having children.

Where this trial is running

Guangzhou, Guangdong

• Gastrointestinal Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Yanhong Deng, Ph.D — Sixth Affiliated Hospital, Sun Yat-sen University
• Study coordinator: Yanhong Deng, Ph.D

Conditions Colorectal Cancer; Neoadjuvant therapy; mFOLFOXIRI; Cadonilimab; mFOLFOX6