Combining radiation and immunotherapy for recurrent rectal cancer

Hypofractionated Radiotherapy Combined With Toripalimab and Chemotherapy +/- Target Therapy for Locally Recurrent Rectal Cancer: a Single-arm, Two-cohort, Phase II Trial (TORCH-R)

This study is testing if combining a special type of radiation with immunotherapy can help people with locally recurrent rectal cancer feel better and improve their chances of surgery and survival.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 93 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, toripalimab, radiation, immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05628038 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial investigates the effectiveness of combining hypofractionated radiotherapy with immunotherapy in patients with locally recurrent rectal cancer. Participants aged 18 to 75 will be divided into two cohorts based on their treatment history and will receive a specific radiation regimen along with toripalimab and chemotherapy. The study aims to evaluate the local objective response rate and other secondary outcomes, including the potential for surgical resection and overall survival. A multidisciplinary team will assess treatment responses and determine further management options.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with confirmed pelvic recurrence of rectal cancer and specific treatment histories.

Not a fit: Patients with extensive distant metastasis or those who have received prior radiotherapy within the last six months may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with recurrent rectal cancer.

How similar studies have performed: Previous studies have shown promising results with similar combinations of immunotherapy and chemoradiotherapy in advanced rectal cancer, indicating potential for success.

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.
* Previous system therapy. Patients Group Cohort A: participants with pelvic recurrence who have not previously been treated with first-line chemotherapy. Cohort B: Patients with disease progression or new lesions after first-line chemotherapy.
* 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.
* 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 Recurrent Rectal Cancer