Short-course radiation with liposomal irinotecan, anti–PD-1, and targeted therapy for locally recurrent rectal cancer

Hypofractionated Radiotherapy Combined With Irinotecan Hydrochloride Liposome, 5-FU, Leucovorin, PD-1 Antibody and Target Therapy in Locally Recurrent Rectal Cancer(NOVELTY-R)

This trial will test whether short-course radiation plus liposomal irinotecan (NALIRIF) with 5‑FU/leucovorin, an anti–PD‑1 drug, and targeted therapy can shrink pelvic recurrences in patients with locally recurrent rectal cancer who have already failed oxaliplatin.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07183865 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm Phase 2 trial combining hypofractionated radiotherapy with eight cycles of NALIRIF (liposomal irinotecan) plus 5‑FU/leucovorin, an anti–PD‑1 antibody, and targeted therapy in patients with locally recurrent rectal cancer. Radiation dosing is short-course (25–40 Gy/5 fractions or 15–30 Gy/5 fractions for re-irradiation of pelvic recurrence) and 25–50 Gy/5 fractions for metastatic sites as needed. The primary endpoint is local objective response rate and secondary endpoints include extrapelvic objective response rate, complete response rate, R0 resection rate, duration of response, progression-free survival, and overall survival. After systemic and local therapy, a multidisciplinary team will decide whether patients proceed to radical surgery or continued systemic/local management.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 years old with MRI/CT-confirmed pelvic recurrence and at least one measurable pelvic lesion by RECIST 1.1, ECOG 0–1, prior failure of oxaliplatin-containing therapy, no radiotherapy within 6 months, no more than five distant lesions in up to three organs, and adequate organ function.

Not a fit: Patients with widespread metastatic disease beyond the allowed lesion/organ limits, poor performance status, recent pelvic radiotherapy (within 6 months), significant organ dysfunction, or pregnancy/lactation are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could increase local tumor shrinkage, raise the chance of curative surgery, and prolong disease control for patients with pelvic recurrence.

How similar studies have performed: Short-course radiotherapy combined with immunotherapy and cytotoxic agents has shown promise in early studies across several solid tumors, but this exact combination with liposomal irinotecan and anti–PD‑1 in locally recurrent rectal cancer is novel.

Eligibility criteria

Inclusion Criteria:

Patient is 18-75 years old at the time of signing the informed consent form. ECOG performance status 0-1. MRI/enhanced CT confirmed pelvic recurrence. According to RECIST 1.1, there is at least one measurable pelvic lesion.

Distant metastasis lesions are no more than 5 and metastatic organ are no more than 3.

No prior radiotherapy within 6 month. Failed to oxaliplatin treatment in prior chemotherapy or chemoradiotherapy due to toxicity or progression.

Has an investigator determined life expectancy of at least 24 weeks. Demonstrate adequate organ function (bone marrow, liver, kidney and clotting function) within 7 days before the first administration without using blood products or hematopoietic stimulating factors.

Non pregnant or lactating patients. Effective contraceptive methods should be used during the study and within 6 months of the last administration.

Fully informed and willing to provide written informed consent for the trial.

Exclusion Criteria:

Previous immunotherapy or Irinotecan Hydrochloride Liposome treatment. Neutrophil \< 1.5×10\^9/L, PLT \< 100×10\^9/L (PLT \< 80×10\^9/L in patients with liver metastasis), or Hb \< 90g/L; blood transfusion within 2 weeks before enrollment is not allowed to meet the enrollment criteria.

TBIL \> 1.5 ULN, or TBIL \> 2.5 ULN in patients with liver metastasis. AST or ALT \> 2.5 ULN, or ALT and / or AST \> 5 ULN in patients with liver metastasis.

Cr \> 1.5 ULN, or creatinine clearance \< 50ml / min (calculated according to Cockcroft Gault formula).

APTT \> 1.5 ULN, PT \> 1.5 ULN (subject to the normal value of the clinical trial research center).

Serious electrolyte abnormalities. Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h. Uncontrolled hypertension: SBP \>140mmHg or DBP \> 90mmHg. The presence of gastrointestinal diseases such as gastric or duodenal active ulcers, ulcerative colitis or unresected tumours with active bleeding; or other conditions likely to cause gastrointestinal bleeding or perforation; or unhealed gastrointestinal perforation or gastrointestinal fistula after surgical treatment.

A history of arterial thrombosis or deep vein thrombosis within 6 months; a history of bleeding or evidence of bleeding tendency within 2 months.

A history of heart disease within 6 months (including congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF\<50%).

Uncontrolled malignant pleural effusion, ascites, or pericardial effusion. The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumour (non-invasive tumour, or carcinoma in situ, or T1).

A history of liver disease including, but not limited to HBV infection or HBV DNA positive(≥1×10\^4/ml), HCV infection or HCV DNA positive(≥1×10\^3/ml) and liver cirrhosis.

Pregnant or lactating women or women who may be pregnant have a positive pregnancy test before the first medication; Or the female participants themselves and their partners who were unwilling to implement strict contraception during the study period.

The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems.

Serious mental abnormalities. The diameter of brain metastasis is greater than 3cm or the total volume is greater than 30cc.

Clinical or radiological evidence of spinal cord compression, or tumours within 3 mm of the spinal cord on MRI.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Zhen Zhang, MD, PhD — Fudan University
• Study coordinator: Zhen Zhang, MD, PhD

Conditions Locally Recurrent Rectal Cancer