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

NCT05359406 | Unknown Phase 2

• 1 other identifier: Miracle-2
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Rectal Cancer; Distal Metastasis

Keywords

anti-PD-1 immunotherapy; short-course radiotherapy

Outcome Measures

Primary Outcomes (1)

• Early Tumor Shrinkage

  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.

  5 years after intervention

Secondary Outcomes (5)

• Disease Control Rate

  5 years after intervention

• Duration of Response

  5 years after intervention

• Overall Survival

  5 years after intervention

• Progression-Free Survival

  5 years after intervention

• Acute toxicity associated with immunotherapy

  from the beginning of the treatment to 90 days after the end of immunotherapy

Study Arms (1)

unresectable group

EXPERIMENTAL

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.

Combination Product: a combination therapy including tislelizumab

Interventions

a combination therapy including tislelizumab COMBINATION_PRODUCT

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.

Also known as: Radiotherapy Followed by Chemotherapy with target therapy and anti-PD-1 immunotherapy

unresectable group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18\~70;
• Patient signs informed consent;
• ECOG score 0\~1;
• Initial colonoscopy and pathology: adenocarcinoma;
• MRI: rectal cancer located less than 10cm from the anus;
• Imaging confirms multiple measurable metastases exist in the liver or lung , which are evaluated as NED unacceptable by MDT discussion;
• no previous treatment;
• Patients have adequate organ function;
• No contraindications to surgery or chemoradiation;
• The relevant test results within 7 days before the first dose must meet the following requirements:
• Blood routine examination (no blood transfusion within 7 days before screening, no correction with hematopoietic stimulating factor drugs):
• Hb≥90g/L
• ANC≥1.5×10\^9/L; LC≥0.5×10\^9/L;
• PLT≥100×10\^9/L;
• WBC≥3.0×10\^9/L, ≤15×10\^9/L;

You may not qualify if:

• Patients will not be accepted into this study if they meet any of the following criteria:
• \. History of tumor-related disease and treatment:
• Age \<18 or \>75 years;
• other malignancy within 5 years, except adequately treated carcinoma in situ of the cervix or squamous cell carcinoma of the skin, or largely controlled basal cell carcinoma of the skin;
• malignant pleural effusion or malignant ascites;
• patients with severe medical comorbidities that preclude radiotherapy and surgery;
• previously treated;
• clinical or radiological evidence of spinal cord compression or a tumor within 3mm of the spinal cord on MRI
• the presence of distant metastases besides the liver and lungs, including brain, bone, ovarian, peritoneal and retroperitoneal multiple lymph node metastases;
• Patients who are considered suitable for using intense systemic treatment to achieve conversion after MDT discussion;
• pathological diagnosis of indolent cell carcinoma;
• patients with microsatellite instability or dMMR;
• patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. that require emergency surgical resection;
• \. Co-morbidities and treatment history:
• Presence of immunodeficiency disorders, including primary immunodeficiency disorders (e.g. caused by genetic factors) or secondary immunodeficiency disorders (e.g. caused by HIV infection or treatment related to immunological agents, etc.);

Sponsors & Collaborators

• LI XIN-XIANG: lead

Study Sites (1)

Xinxiang Li

Shanghai, Shanghai Municipality, 200032, China

Location

Central Study Contacts

Xinxiang Li, MD

CONTACT

+862164175590; lxx1449@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 28, 2022
• First Posted: May 3, 2022
• Study Start: December 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 15, 2022

Record last verified: 2022-11

Locations

CN (1)