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

NCT05359393 | Not Yet Recruiting Phase 2

• 1 other identifier: Miracle-1
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Rectal Cancer; Liver Metastasis; Pulmonary Metastasis; Microsatellite Stable Colorectal Carcinoma

Outcome Measures

Primary Outcomes (1)

• NED rate

  rate of no evidence of disease for one year

  1 years after treatment

Secondary Outcomes (6)

• Overall Survival

  5 years after surgery

• Disease Free Survival

  5 years after surgery

• Local Recurrence

  5 years after surgery

• Objective Response Rate

  5 years after surgery

• Tumor Regression Rate

  5 years after surgery

Study Arms (1)

resectable group

EXPERIMENTAL

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.

Combination Product: a combination therapy including tislelizumab

Interventions

a combination therapy including tislelizumab COMBINATION_PRODUCT

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).

Also known as: preoperative radiotherapy combined with immunotherapy and chemotherapy

resectable group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18\~75;
• 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 that there are measurable metastases in the liver or lung, which are evaluated as NED acceptable 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

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Interventions

Immunotherapy; Drug Therapy

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Central Study Contacts

Xinxiang Li, MD

CONTACT

86-21-64175590; 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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 28, 2022
• First Posted: May 3, 2022
• Study Start: December 1, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: November 14, 2022

Record last verified: 2022-11

Locations

CN (1)