The goal of this clinical trial is to see if high- and low-dose radiotherapy combined with immunotherapy can work in patients with advanced gastric, colorectal, and ovarian cancers with peritoneal metastases, and to learn about the safety of this new combination treatment modality. The main questions they aim to answer are: * Can whole-abdominal low-dose radiotherapy (LDRT) combined with selected-site stereotactic body radiation therapy (SBRT) followed by Cadonilimab control peritoneal lesions and malignant ascites in patients with advanced solid tumors with peritoneal metastases? * Can the novel treatment modality of high- and low-dose radiotherapy combined with immunotherapy produce a survival benefit in patients with advanced gastric, colorectal, and ovarian cancers who have received multiple lines of therapy? * Is the safety profile of this new treatment modality acceptable? Participants will: * Receive stereotactic body radiation therapy (SBRT) to selected sites and low-dose radiotherapy (LDRT) to the whole abdomen, followed by bi-weekly treatment with Cadonilimab until disease progression, death, toxicity intolerance or withdrawal of informed consent. * Receive whole body imaging and laboratory tests every 6-8 weeks to assess the efficacy of tumor treatment.
Several studies have confirmed that the prognosis for advanced solid tumors for which there is no longer a standard of care is extremely poor, with optimal supportive care and an overall survival time of usually 1-5 months, and better treatment options are urgently needed to benefit patients' survival. For advanced solid tumors with peritoneal metastases, the prognosis is even worse. The peritoneal metastatic lesions respond poorly to chemotherapy, targeting, immunotherapy, surgical treatment, and other currently used treatments, and the expected survival time is short, so there is an urgent need to seek more effective treatment modalities. There is a synergistic effect between radiotherapy and immunotherapy, and several studies have explored the combination of radiotherapy and immune checkpoint inhibitors in the treatment of solid tumors, and the results have shown that this combination regimen has a good anti-tumor effect, but the optimal radiotherapy modality and dose of radiotherapy are still in the exploratory stage. At present, some preclinical studies and small sample studies have shown that the combination of high- and low-dose radiotherapy can change the tumor immune microenvironment, reverse the state of immunosuppression, and play a strong anti-tumor effect in combination with immune checkpoint inhibitors. Therefore, the investigators propose to conduct a single-arm, prospective clinical study of whole-abdominal low-dose radiotherapy (LDRT) combined with stereotactic body radiation therapy (SBRT) followed by Cadonilimab for the treatment of advanced gastric, colorectal, and ovarian cancers with peritoneal metastases. The study evaluates the efficacy of this combination therapy modality on peritoneal metastatic lesions, as well as the objective remission rate (ORR), disease control rate (DCR), duration of remission (DoR), progression-free survival (PFS), overall survival (OS), and safety of the patients. Our study aims to further explore the combination treatment options to improve the efficacy and prognosis of backline treatment for advanced tumors, and to provide more evidence for the clinical practice of radiotherapy combined with immunotherapy in advanced gastric, colorectal, and ovarian cancers with peritoneal metastases.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Radiation: Stereotactic Body Radiation Therapy (SBRT) * Stereotactic Body Radiation Therapy (SBRT) will be performed first at a total dose of 20-50 Gy, delivered in 3-5 fractions of 6-10 Gy each. And the target area was specifically selected based on the location and size of the patient's tumor. Radiation: low-dose radiotherapy (LDRT) * Whole-abdominal low-dose radiotherapy will be initiated within 10 days of the end of SBRT with a total dose of 7-15 Gy at 0.5-2.0 Gy twice daily. And the target area included all suspicious tumor tissues and potential metastatic foci in the abdominal cavity.
· Cadonilimab: 6 mg/kg IV, D1, Q2W, until disease progression, death, toxicity intolerance or withdrawal of informed consent
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, China
Peritoneal response rate
The Peritoneal Cancer Index (PCI) score is currently the most commonly used and validated tool for assessing the extent of peritoneal metastasis and prognosis. The method is to divide the abdominal cavity into 9 partitions, the small intestine into 4 partitions, a total of 13 partitions, and each partition is assigned a score of 0\~3 according to the lesion size (LS) seen intraoperatively. That is, the LS score for each of the 13 divisions was determined by intraoperative or radiologic imaging, with a total score of 39 points. In this study, imaging evaluations were performed every 8 weeks to assess the efficacy of peritoneal tumor lesions by abdominal DWI + T2 MRI or abdominal CT enhancement. PCI scores ranged from 0\~39, with higher scores implying more peritoneal metastatic lesions. The peritoneal response was evaluated as effective if the PCI score decreased compared with baseline, stable if the PCI score remained unchanged, and ineffective if the PCI score increased.
Time frame: within 3 years after primary treatment
Objective response rate (ORR)
The proportion of all subjects treated in the study who had a best overall response (BOR) of complete remission (CR) or partial remission (PR) according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) .
Time frame: within 3 years after primary treatment
Disease Control Rate (DCR)
The proportion of all subjects receiving study treatment who have a best overall response (BOR) of complete remission (CR), partial remission (PR), or stable disease (SD) as assessed by RECIST version 1.1. If CR or PR is achieved, subjects must be confirmed no less than 4 weeks (28 days) after the initial evaluation.
Time frame: within 3 years after primary treatment
Duration of Response (DoR)
The time from the first recording of confirmed remission (CR or PR) to the time of the first recording of disease progression (according to RECIST version 1.1) or death due to any cause, whichever occurs first. For those subjects who are alive and without disease progression at the time of analysis data cut-off, censoring will be performed on the date of the final tumor determination. DoR will be evaluated only for subjects who achieved a confirmed remission CR or PR.
Time frame: within 3 years after primary treatment
Progression-free survival (PFS)
Defined as the subject from enrollment to the date of the first documented tumor progression or the date of death from any cause, whichever occurs first.
Time frame: within 3 years after primary treatment
Overall Survival (OS)
Overall Survival (OS) was defined as the time between the start of enrollment and the death of the subject due to all causes. The OS of subjects who were alive at the last follow-up visit was counted as data censored at the time of the last follow-up visit. The OS of subjects who were lost to follow-up was counted as data censored at the time of last confirmed survival prior to the loss of follow-up. OS for data censoring was defined as the time from randomization grouping to censoring.
Time frame: within 3 years after primary treatment
Adverse events (AEs)
The safety parameters in this study included clinical symptoms, vital signs, physical examination, and laboratory tests. Observed adverse events (AEs) were evaluated with reference to the National Cancer Institute (NCI) AE Common Terminology Criteria Version 5.0 (NCI CTCAE Version 5.0), including type, incidence, severity, time of onset and end, whether it was a serious adverse event, relevance to the study drug, and regression.
Time frame: within 3 years after primary treatment
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