| Eligibility |
Inclusion Criteria:
1. Histologically or cytologically confirmed cervical cancer, with recurrence or
metastasis after previous systemic surgery, postoperative chemoradiotherapy, or
radical chemoradiotherapy, and suitable for local radiotherapy (non-central pelvic
recurrence or oligometastasis in stage IVB).
2. Pathologically and radiologically confirmed tumor with maximum diameter not exceeding
the maximum diameter for particle treatment (5-7cm).
3. Age =18 years and =70 years, female at the time of signing the informed consent.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, able to tolerate
puncture.
5. Measurable lesions according to RECIST 1.1, with target lesions unsuitable for
surgical treatment.
6. Expected survival time of more than 3 months.
7. Adequate organ function as per standard criteria for immunotherapy:
- Absolute neutrophil count (ANC) =1.5×109/L
- Platelets =75×109/L
- Hemoglobin =90 g/L
- Serum albumin =30 g/L
- Total bilirubin (TBil) =1.5×ULN
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =2.5×ULN; if
there is liver metastasis, ALT and AST <5×ULN
- Serum creatinine =1.5×ULN
- Blood urea nitrogen (BUN) =2.5×ULN
- Thyroid-stimulating hormone (TSH) = upper limit of normal (ULN); if abnormal,
investigate T3 and T4 levels, and if T3 and T4 levels are normal, the patient may
be eligible.
8. Female subjects of childbearing potential must have a negative serum pregnancy test
within 3 days before starting study drug and agree to use a medically acceptable
method of contraception during the study and for 3 months after the last dose of study
drug.
9. Signed informed consent and the subject must understand the purpose of the study and
the requirements for participation and voluntarily agree to participate.
Exclusion Criteria:
Potential subjects who meet any of the following criteria should be excluded from the
study:
1. History of using anti-PD-1 antibodies, anti-CTLA-4 antibodies, TCR-T, CAR-T, or other
immunotherapy within the past 4 weeks before the first dose, or participation in other
anti-tumor drug clinical trials within the past 4 weeks before the first dose, or
planned use of attenuated live vaccines during the study period.
2. Diagnosis of any other malignant tumor within the past 3 years.
3. Use the first dose, excluding intranasal and inhaled corticosteroids or physiologic
doses of systemic corticosteroids (not exceeding 10 mg/day prednisolone or
equivalent).
4. Patients with symptomatic, visceral metastasis, or short-term life-threatening
complications risk, including uncontrollable large effusions (pleural, pericardial, or
peritoneal), lymphangitis carcinomatosis, and 30% or more liver involvement.
5. Presence of any active autoimmune disease or history of autoimmune disease, including
but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis,
hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism.
Patients with vitiligo or childhood asthma that has been completely resolved without
any intervention during adulthood can be included. Patients with asthma requiring
bronchodilators for medical intervention cannot be included.
6. Uncontrolled hypertension (systolic blood pressure =140 mmHg or diastolic blood
pressure =90 mmHg despite optimal medical management).
7. Grade II or higher myocardial ischemia or myocardial infarction, uncontrolled
arrhythmia (including QTc interval =450 ms for males or =470 ms for females), NYHA
class III-IV heart failure, left ventricular ejection fraction (LVEF) <50% as
determined by echocardiography. Patients who experienced myocardial infarction, New
York Heart Association class II or higher heart failure, uncontrolled angina,
uncontrolled severe ventricular arrhythmia, clinically significant pericardial
disease, or acute ischemia or active conduction system abnormalities based on
electrocardiogram within 6 months before enrollment.
8. Coagulation abnormalities (INR >1.5 or prothrombin time (PT) > upper limit of normal
(ULN) + 4 seconds or APTT >1.5 ULN), bleeding tendency, or receiving thrombolysis or
anticoagulation therapy.
9. Presence of obvious hemoptysis or expectoration of at least half a teaspoon (2.5 ml)
of blood within 2 months before enrollment; or occurrence of significant clinically
relevant bleeding symptoms or clear bleeding tendency, such as gastrointestinal
bleeding, bleeding gastric ulcer, baseline occult blood++ in stool, or vasculitis
within 3 months before enrollment; or occurrence of arterial/venous thromboembolic
events, such as cerebrovascular accident (including transient ischemic attack,
cerebral hemorrhage, or cerebral infarction), deep vein thrombosis, or pulmonary
embolism within 6 months before enrollment.
10. Severe infection within 4 weeks before the first dose (e.g., requiring intravenous
administration of antibiotics, antifungals, or antiviral agents), or unexplained fever
>38.5°C during screening or within 4 weeks before the first dose.
11. History of substance abuse, inability to discontinue substance abuse or presence of
psychiatric disorders.
12. Major surgery within 4 weeks before the first dose or presence of open wounds or
fractures.
13. Factors significantly affecting oral drug absorption, such as inability to swallow,
chronic diarrhea, or intestinal obstruction; or occurrence of fistula or perforation
of hollow organs within 6 months.
14. Urinalysis showing urine protein =++, or confirmed 24-hour urine protein =1.0 g.
15. Human immunodeficiency virus (HIV) infection or known acquired immune deficiency
syndrome (AIDS), active hepatitis B (HBV DNA =500 IU/ml), hepatitis C (positive HCV
antibodies and HCV-RNA above the detection limit of the assay), or concurrent
infection with both hepatitis B and hepatitis C.
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