Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasm Metastasis

Rectal Neoplasms

Neoplastic Processes

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Antibodies

Antibodies, Monoclonal

Tislelizumab

Immunomodulating Agents

Immunoglobulins

Liver Extracts

Antineoplastic Agents, Immunological

Patients will receive tislelizumab in combination with radiotherapy and targeted therapy. 2 weeks after large fractionated radiotherapy for primary rectum lesion and metastasis, patients will be treated with systemic treatment including chemotherapy combined with targeted therapy and immunotherapy. Patients will be evaluated by MDT every 2 months since the beginning of the treatment. Those who are regarded as NED will be treated surgically/locally. Those in stable or partial remission will continue with combination therapy. Those with progressive disease will be withdrawn from study. Patients who are not surgically treatable will continue with combination therapy until disease progression or receiving surgical treatment.

For liver/pulmonary metastasis, the treatment plan is to implement large fraction radiotherapy for 4-8 times. For primary rectum lesion, short-course radiotherapy regimen through intensity-modulated radiotherapy will be applied with dose of 25Gy/5Fx. Immunotherapy contains anti-PD-1 monoclonal antibody, Tislelizumab(200mg, d1, q3w, i.v). For patients with RAS or BRAF mutation, chemotherapy adopts FOLFOX+BEV plan. For patients without RAS or BRAF mutation, chemotherapy adopts FOLFIRI+CET plan.

Patients will be followed for safety during the study. The safety follow-up period is defined as 90 days after the last dose of tislelizumab. Safety related data will be collected from the time of signing the informed consent until the end of the safety follow-up period or the start of new therapy.

a combination therapy including tislelizumab

Xinxiang Li, MD

Though surgical resection remains the primary choice for advanced rectal cancer, about 80% are considered unresectable due to the number, size, or location of metastases. The overall prognosis of patients who accepted traditional treatment methods is still poor. Therefore, the investigators designed a combination therapy, short-course radiotherapy followed by chemotherapy with target therapy and anti-PD-1 immunotherapy. This study implement the combination therapy in patients with rectal cancer who are initially unresectable in the locally advanced stage with multiple liver/pulmonary metastases, to evaluate whether they can improve the objective response rate, the conversion rate of radical surgery and prolong the overall survival of patients, and strive to provide high-level medical evidence for the clinical treatment.

A Combination Therapy Including Anti-PD-1 Immunotherapy in Rectal Cancer With Refractory Distal Metastasis

Radiotherapy Followed by Chemotherapy With Target Therapy and Anti-PD-1 Immunotherapy in Locally Advanced Rectal Cancer With Refractory Liver Metastasis/Pulmonary Metastasis(Miracle-2): A Prospective, Single Arm, Multi-Center, Phase II Clinical Trial

The relative change of the sum of the longest diameters of the baseline RECIST target lesion at 8 weeks of systemic therapy, distinguished by 20% as the cut-off point between early response and no response.

Percentage of patients with disease control in non-irradiated metastatic lesions

The time between PR/CR and subsequent progressive disease or death of any cause.

The time from the beginning of treatment to the date of death.

The time from the start of treatment to PD or death of any cause.

Proportion of patients with treatment-related acute toxicity.

LI XIN-XIANG

Professor

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Neoplasms, Second Primary

Lung Neoplasms

Colonic Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Oxaliplatin

Capecitabine

In this group, we propose a combination therapy, preoperative short-course radiotherapy followed by neoadjuvant chemotherapy and anti-PD-1 immunotherapy, for microsatellite-stable patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis.

Patients will receive tislelizumab in combination with neoadjuvant radiotherapy and chemotherapy, and will be evaluated 2-3 weeks after completion of the treatment. Those patients who achieve complete clinical regression of the lesion can choose observation, but for those without CCR, surgical resection (TME of the primary lesion, surgical resection of metastases or other destructive local treatment) will be applied. Patients will continue to receive tislelizumab for one year after surgery or during observation.

For liver/pulmonary metastasis, the treatment plan is to implement large fraction radiotherapy for 4-8 times. For primary rectum lesion, short-course radiotherapy regimen through intensity-modulated radiotherapy will be applied with dose of 25Gy/5Fx.

Immunotherapy contains anti-PD-1 monoclonal antibody, Tislelizumab(200mg, d1, q3w x6, i.v). Chemotherapy adopts CAPEOX plan, including Capecitabine(1000mg/m2 bid, d1-14, p.o) and oxaliplatin(130mg/m2, d1, i.v).

Although patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis could benefit from surgery resection, these patients still have a poorer prognosis compared to those without distal metastasis. Based on previous studies, there is no confirmation of whether these patients could benefit from preoperative immunotherapy combined with conventional chemoradiotherapy. This study proposes a combination therapy, preoperative short-course radiotherapy followed by neoadjuvant chemotherapy and anti-PD-1 immunotherapy, for microsatellite-stable patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis, to assess its impact on tumor retreat, decline of postoperative metastasis and recurrence, and the disease-free survival and overall survival of patients. Besides, this study will provide high-level medical evidence for future clinical treatment of patients with advanced rectal cancer.

A Combination Therapy Including Anti-PD-1 Immunotherapy in MSS Rectal Cancer With Resectable Distal Metastasis

Radiotherapy Followed by Chemotherapy and Anti-PD-1 Immunotherapy in MSS Rectal Cancer With Resectable Liver/ Pulmonary Metastasis(Miracle-1): A Prospective, Single Arm, Multi-Center, Phase II Clinical Trial

rate of no evidence of disease for one year

For patients who still survive when the final analysis takes place, the date of the last 1 contact will be recorded.

DFS refers to the period of time between the date of surgery and the day of the patient's tumor recurrence or death (earliest occurrence).

The date of recurrence is defined as the date on which an objective examination yields a positive result.

Percentage of patients with objective response to primary or metastatic lesions

Surgical excision specimens are taken every 1 cm, and the sections are given to at least 2 pathologists for independent scoring

According to the NCI CTCAE v5.0 assessment, the proportion of patients with treatment-related acute toxicity developed from the beginning of treatment to 90 days after the end of immunotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Combination Therapy Including Anti-PD-1 Immunotherapy in Rectal Cancer With Refractory Distal Metastasis	NCT05359406	Advanced Rectal... Distal Metastas...	a combination t...	18 Years - 70 Years	Fudan University
A Combination Therapy Including Anti-PD-1 Immunotherapy in MSS Rectal Cancer With Resectable Distal Metastasis	NCT05359393	Advanced Rectal... Liver Metastasi... Pulmonary Metas... Microsatellite ...	a combination t...	18 Years - 75 Years	Fudan University
A Combination Therapy Including Anti-PD-1 Immunotherapy in Rectal Cancer With Refractory Distal Metastasis	NCT05359406	Advanced Rectal... Distal Metastas...	a combination t...	18 Years - 70 Years	Fudan University

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