MRIMR-2: A Combination Therapy Including Anti-PD-1 Immunotherapy in Rectal Cancer With Refractory Distal Metastasis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: unresectable group In this group, patients with rectal cancer who are initially unresectable in the locally advanced stage with distant multiple metastases receive a combination therapy, short-course radiotherapy combined with chemotherapy and targeted therapy combined with immunotherapy. |
Combination Product: a combination therapy
Patients will be given short-course radiotherapy, sequential anti-PD-1 monoclonal immunotherapy and FOLFIRI or mFOLFOX6 plus cetuximab or bevacizumab chemotherapy. The progression of cancer will be evaluated every three months to discuss whether NED is acceptable by MDT. Surgical treatment is pursued, and combination therapy will be continued in inoperable patients until accepting surgery or the disease progresses so that patients withdraw from the study.
We implement SABR on liver/pulmonary metastasis. Drugs include Tislelizumab, mFOLFOX6/FOLFIRI plan and cetuximab/bevacizumab. After surgery, the combination therapy of immunotherapy, chemotherapy and target therapy will be continued.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate [2 years after intervention]
Percentage of patients with objective response to non-irradiated metastatic lesions.
Secondary Outcome Measures
- Disease Control Rate [2 years after intervention]
Percentage of patients with disease control in non-irradiated metastatic lesions
- Duration of Response [2 years after intervention]
The time between PR/CR and subsequent progressive disease or death of any cause.
- Overall Survival [3 years after intervention]
The time from the beginning of treatment to the date of death.
- Progression-Free Survival [2 years after intervention]
The time from the start of treatment to PD or death of any cause.
- Acute toxicity associated with immunotherapy [from the beginning of the treatment to 90 days after the end of immunotherapy]
Proportion of patients with treatment-related acute toxicity.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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, cT3-T4b, N+;
-
Imaging confirms multiple measurable metastases exist in the liver or lung , which are evaluated as NED unacceptable by MDT discussion;
-
Liver or lung metastases can be treated with radiation therapy, but it must be ensured that one metastasis is not irradiated for evaluation;
-
no previous treatment;
-
Patients have adequate organ function;
-
No contraindications to surgery or chemoradiation;
-
Expected survival time >6 months;
-
The gene status of KRAS, NRAS, BRAF and HER2 is clear;
-
Patients are willing and able to follow the protocol during the study, including receiving treatment and scheduled follow-up and examination.
Exclusion Criteria:
-
Age <18 or >70;
-
Pregnant or lactating women;
-
Other malignant tumors within 5 years, except for adequately treated cervical carcinoma in situ or cutaneous squamous cell carcinoma, or basically controlled cutaneous basal cell carcinoma;
-
Patients with severe medical comorbidities that prevent chemoradiotherapy and surgery;
-
Malignant thoracic ascites;
-
Previous treatment;
-
Clinical or radiological evidence of spinal cord compression, or tumors within 3mm of the upper MRI spinal cord;
-
Distant metastases except for the liver or lungs, or multiple metastases to the liver and lungs that cannot be achieved by MDT evaluation;
-
Pathological diagnosis is incinerated cell carcinoma;
-
Patients who receive systemic steroid therapy (>10 mg/d or equivalent dose) at the same time of the trial;
-
Patients with an active, known or suspected autoimmune disease, hypothyroidism requiring hormone replacement therapy, and skin conditions that did not require systemic treatment (such as vitiligo, psoriasis, or hair loss) can be selected;
-
History of active tuberculosis bacilli disease;
-
Patients had a serious active infection requiring intravenous antibiotic therapy during admission;
-
Vaccinated or prepared to receive live vaccines within 30 days prior to immunotherapy;
-
Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, and other conditions requiring emergency surgical resection;
-
Severe mental illness;
-
Patients or family members who can not understand the conditions and objectives of this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Xinxiang Li | Shanghai | Shanghai | China | 200032 |
Sponsors and Collaborators
- LI XIN-XIANG
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MRIMR-2