The Combination of Hypofractionated Radiotherapy and Immunotherapy in Locally Recurrent Rectal Cancer

• Status: Not yet recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The study is a prospective, single-center, single-arm phase II clinical trial to evaluate the combination of preoperative (re)irradiation, chemotherapy and immunotherapy in locally recurrent rectal cancer. The primary endpoint is the R0 resection rate of pelvic recurrent tumour. The secondary endpoints include the overall response rate (ORR), progression-free survival (PFS), local recurrence free survival (LRFS), overall survival (OS), safety and tolerability.

The enrolled patients will receive 25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history), 6 cycles of toripalimab and CAPOX, and followed by multidisciplinary team (MDT) for decision: radical surgery, sustained treatment until resectable or exit. The study protocol was approved by the Ethics Committee of FUSCC. All patients provided written informed consent before recruitment. Shanghai Junshi Biomedical Technology Co., Ltd. Provides the first three cycles of toripalimab for free and has purchased liability insurance for clinical trial subjects.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fudan University
• Treatments: Antibodies; Capecitabine; Oxaliplatin

Criteria

Inclusion Criteria:

• Aged over 18 years old, regardless of gender.

• Histologically or cytologically or iconography confirmed locally recurrent rectal cancer with or without distant metastasis (UICC 8th version).

• No prior radiotherapy within 6 month.

• Distant metastasis lesions are resectable by MDT evaluation.

• Has at least 1 measurable oligometastatic lesions on imaging (RECIST version 1.1).

• ECOG performance status 0-1.

• 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:

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.

• History of anti-PD-1, PD-L1, PD-L2, CTLA-4 or any other specific T cell co-stimulation or checkpoint pathway targeted therapy.

• Receiving anti-VEGF or anti-EGFR therapy within 4 weeks.

• 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.