Irinotecan Liposomes in Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer (CinClare-2)

University of Chinese Academy Sciences

Status and phase: Not yet enrolling; Phase 3

Conditions: Locally Advanced Rectal Cancer

Treatments: Drug: FOLFOX; Drug: NALIRI; Radiation: LCRT

Study type: Interventional

Funder types: Other

Identifiers

NCT07074353

CinClare-2

Details and patient eligibility

About

This study enrolled patients with locally advanced rectal cancer. The experimental group received irinotecan liposomes combined with standard total neoadjuvant therapy (TNT), while the control group received standard TNT. The study endpoints were the complete response rate (cCR + pCR), 3-year event-free survival (EFS) rate, and overall survival (OS). The aim was to compare the efficacy and safety of irinotecan liposomes combined with or without standard TNT.

Enrollment: 360 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years and ≤ 75 years, both male and female are eligible;
2. Histologically confirmed rectal adenocarcinoma;
3. Clinical stage assessed by MRI as T3-4 or N+ (according to the 8th edition of the AJCC);
4. Distance from the lower edge of the tumor to the anal verge ≤ 10 cm;
5. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1;
6. UGT1A1*6 and UGT1A1*28 gene phenotypes are either wild-type (GG+6/6) or single-site mutant (GG+6/7 or GA+6/6);
7. No prior anti-tumor treatment for rectal cancer, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.;
8. Normal function of major organs.

Exclusion criteria

1. Previous or ongoing treatment for rectal cancer, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
2. Known MSI-H (high microsatellite instability) by genetic testing or dMMR (deficient mismatch repair) by immunohistochemistry.
3. Known hypersensitivity, allergic reaction, or contraindication to irinotecan liposomes/vehicle, irinotecan, other liposomal products, 5-FU, leucovorin, oxaliplatin, or any of these agents.
4. Uncontrolled cardiac symptoms or disease.
5. Severe infection (CTCAE > Grade 2) within 4 weeks prior to the first use of the study drug, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; baseline chest imaging showing active pulmonary inflammation; signs and symptoms of infection within 14 days prior to the first use of the study drug or requiring oral or intravenous antibiotic therapy, excluding prophylactic use of antibiotics.
6. Severe gastrointestinal dysfunction (inflammation or diarrhea greater than Grade 1).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

360 participants in 2 patient groups, including a placebo group

NALIRI-TNT

Experimental group

Description:

Irinotecan Liposomes+Long-course concurrent chemoradiotherapy followed by consolidation chemotherapy

Treatment:

Radiation: LCRT

Drug: NALIRI

Drug: FOLFOX

TNT

Placebo Comparator group

Description:

Long-course concurrent chemoradiotherapy followed by consolidation chemotherapy

Treatment:

Radiation: LCRT

Drug: FOLFOX