Using a combination of drugs to treat locally advanced colorectal cancer

Phase II Study of Nanoliposomal Irinotecan, Oxaliplatin Plus Capecitabine As Conversion Therapy for Patients with Locally Advanced Colorectal Cancer

This study is testing if a new combination of drugs can shrink locally advanced colorectal cancer tumors enough to make them operable for surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Beijing)
• Trial ID: NCT06405139 on ClinicalTrials.gov

What this trial studies

This study investigates the efficacy and safety of a novel conversion therapy for locally advanced colorectal cancer using a combination of nanoliposomal irinotecan, oxaliplatin, and capecitabine. Patients will receive a modified FOLFOXIRI regimen over a series of cycles, with evaluations for treatment effectiveness and potential surgical resection after every four cycles. The goal is to determine if this combination can make previously unresectable tumors operable, thereby improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with histopathologically confirmed locally advanced colorectal cancer that is not amenable to radiotherapy.

Not a fit: Patients with colorectal cancer that has already been treated with systemic therapy or those with a poor prognosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients with locally advanced colorectal cancer, potentially making their tumors resectable.

How similar studies have performed: While neoadjuvant chemotherapy has been successful in other cancer types, the specific approach of using this combination for locally advanced colorectal cancer is still exploratory.

Eligibility criteria

Inclusion Criteria:

1. With a full understanding of the study, each participant volunteered to participate in this study and signed the informed consent (ICF) with good compliance and follow-up.
2. Age ≥18 and ≤70.
3. ECOG physical status score is 0 or 1.
4. Expected survival period ≥ 12 weeks.
5. Patients with histopathological confirmed MSS/pMMR-type adenocarcinoma of the colon and upper rectum which is not amenable to radiotherapy.
6. R0 resection was expected to be achieved by necessarily combined organ resection, or R0 resection cannot be achieved, assessed by CT and/or MRI and multidisciplinary team (MDT) discussion.
7. The clinical stage was cT4N1-2M0 or cT4bN0M0 according to AJCC 8th edition.
8. Patients with multiple primary colorectal cancer are eligible, if one of the primary tumors meets the inclusion criteria.
9. Patients with intestinal obstruction was relieved by colonic stenting or ostomy.
10. Patients had not received systematic therapy, such as surgery, chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
11. At least one evaluable lesion (according to RECIST v1.1 standard);
12. Adequate organ function according to the following laboratory test values:

    1. Hemoglobin value ≥90g/L.
    2. White blood cell count ≥3.5\*109/L.
    3. Absolute neutrophil count ≥1.5\*109/L.
    4. Platelet count ≥100\*109/L.
    5. Serum creatinine ≤ upper limit of normal (ULN) or creatinine clearance ≥60ml/min.
    6. Total serum bilirubin ≤1.5 upper normal limit (ULN).
    7. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5 upper limit of normal value (ULN).
13. Women with reproductive potential (\< 2 years after the last menstrual period) and men use effective contraceptive methods until half a year after the last treatment.

Exclusion Criteria:

1. Patients who had shown hypersensitivity to the test drugs or other liposomal products.
2. Patients who have participated in other clinical trials in the past 4 weeks.
3. Previous or concurrent cancer diagnosed within 5 years (except cured basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix; the treatment of other malignant tumors has been completed for more than 5 years, and there is no clinical and imaging evidence of recurrence or progression except).
4. dMMR/MSI-H-type colorectal cancer.
5. Symptomatic peripheral neuropathy ≥ grade 2 (CTCAE 5.0).
6. Patients unable to swallow or lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
7. Patients had severe bleeding (CTCAE 5.0 grade ≥3) in the previous 4 weeks.
8. History of abdominal fistula, gastrointestinal perforation, intestinal obstruction, chronic diarrhea, or inflammatory bowel disease including Crohn's disease and ulcerative colitis within 6 months prior to the first study treatment.
9. Patients with interstitial lung disease, except only imaging demonstrated interstitial lung disease without symptoms.
10. Uncontrolled central nervous system metastasis (symptomatic or metastatic sites are midbrain, pons, medulla, or spinal cord) or other central nervous system diseases.
11. Received strong inhibitors or inducers of CYP3A4 and CYP2C8, or strong inhibitors of UGT1A1 in the previous 2 weeks.
12. Uncontrolled hypertension by a single-antihypertensive medication (systolic blood pressure \>140 mmHg or diastolic pressure \>90 mmHg). Patients with severe cardiac dysfunction, such as LVEF\< 50%, CHF≥ grade 2, severe/unstable angina, history of stroke or transient ischemic attack or myocardial infarction in the previous 6 months. Patients with a history of ventricular tachycardia, torsades de pointes, prolonged QTc, complete left bundle branch block, or third-degree atrioventricular conduction block.
13. Abnormal blood coagulation function, bleeding tendency or receiving thrombolysis or anticoagulant therapy.
14. Patients of childbearing potential are unwilling to practice contraception.
15. Patients with active hepatitis B, hepatitis C, syphilis, or human immunodeficiency virus infection.
16. Patients with current active infections require anti-infection treatment within 2 weeks of starting study treatment.
17. History of a definite neurological or mental disorder, including epilepsy and dementia.
18. Patients with any clinically significant disease, metabolic disorders, or laboratory abnormality. The investigator could reasonably consider those patients not suitable for the study, affecting the analysis of the results or putting those patients at high risk.

Where this trial is running

Beijing

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Lin Yang — Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
• Study coordinator: Lin Yang

Conditions Colorectal Cancer; Locally Advanced Colorectal Cancer; Nanoliposomal Irinotecan; Oxaliplatin; Capecitabine; Conversion Therapy