| Eligibility |
Inclusion Criteria:
- 1) Prospective participants will be voluntarily enrolled in this research study and
will provide written informed consent, demonstrating the ability to adhere to
scheduled visits and associated procedures.
2) Individuals aged between 18 and 75 years old are eligible for inclusion. 3)
Patients with histologically or cytologically confirmed cervical squamous cell
carcinoma, along with documented disease progression that is unresponsive to curative
treatment. It should be noted that confirmation of the original primary tumor tissue
by a pathological report is required.
4) Ineligibility due to failure of standard systemic treatment for persistent,
recurrent, or metastatic cervical cancer (defined as progression or recurrence within
six months after at least one cycle of standard systemic treatment; patients who have
previously received anti-PD-1/PD-L1 antibody treatment and achieved CR, PR, or SD=6
months may still be considered).
5) Not suitable for local treatments such as curative surgery or radiotherapy. 6) A
minimum interval of four weeks must occur between the completion of prior systemic
therapy and administration of the investigational drug. Additionally, any
treatment-related adverse events must have resolved to CTCAE V5.0 grade =1 (excluding
hair loss and fatigue).
7) At least one measurable lesion must serve as a target lesion according to RECIST
V1.1 criteria.
8) Presence of at least one non-target lesion amenable to SBRT is also necessary.
9) Eastern Cooperative Oncology Group Performance Status (ECOG PS) score should be
either 0 or 1.
10)Expected survival time should exceed 12 weeks 11)Female subjects capable of
reproduction need to utilize effective contraception throughout the study period and
for at least five months following their final dose of the investigational drug
12)Subjects are required to consent providing sufficient tumor tissue samples for EGFR
expression detection including archived tumor samples (paraffin blocks or an adequate
number of unstained slides meeting study requirements); if no archived tumor tissue
samples are available, subjects must agree on biopsy from the tumor site 13)Good organ
function and bone marrow hematopoietic function.
Exclusion Criteria:
1. Diagnosed with malignancies other than basal cell carcinoma, squamous cell carcinoma
of the skin, in situ carcinoma cured by surgical resection, and/or papillary thyroid
carcinoma cured by surgery within 5 years prior to the initial dose. Participants must
have pathological types other than cervical squamous cell carcinoma.
2. Participants presenting with clinical symptoms or requiring drainage due to pleural
effusion, ascites, or pericardial effusion are eligible for inclusion, except those
whose effusion does not require drainage or ceases draining within 3 days without a
significant increase.
3. Participants who are scheduled for or have previously undergone organ or bone marrow
transplantation.
4. Individuals with acute or chronic active hepatitis B or C infection, who have HBV DNA
levels greater than 200IU/ml or 103 copies/ml, or are positive for anti-HCV antibodies
with HCV-RNA levels above the detection limit may be eligible. Additionally,
individuals with acute or chronic active hepatitis B or C infection who have been
treated with nucleoside analog antiviral agents and have HBV DNA or HCV-RNA levels
below the specified criteria or below the detection limit may also be eligible.
5. Individuals with meningeal metastasis or symptomatic central nervous system (CNS)
metastasis may be considered for this study. Furthermore, individuals with
asymptomatic brain metastasis that has been treated and symptoms stabilized for at
least 2 weeks may also qualify if they meet specific criteria: presence of measurable
lesions outside of the CNS; absence of metastasis to certain areas within the brain;
no history of intracranial hemorrhage; discontinuation of hormone therapy at least 14
days prior to receiving the first dose of study drug.
6. Any life-threatening bleeding event within the past 3 months, including the
requirement for blood transfusion, surgical intervention or local treatment, or
ongoing pharmacological therapy.
7. Any arterial thrombosis, embolism, or ischemia within the past 6 months, such as
myocardial infarction, unstable angina, or cerebrovascular accident. A history of any
significant thromboembolic event within the past 3 months, such as deep vein
thrombosis or any other thromboembolic event (thrombosis related to a portacatheter or
central venous catheter insertion site, superficial vein thrombosis, or a stable
post-treatment thrombosis is not considered "significant" thromboembolic event).
8. Hepatic vein thrombus involving both the hepatic trunk and the left and right
branches, or involving both the trunk and the superior mesenteric vein, inferior vena
cava; superior vena cava thrombus, superior vena cava syndrome.
9. Tumor invasion of surrounding important organs or blood vessels (such as the great
vessels of the mediastinum, the superior vena cava, the inferior vena cava, the
abdominal aorta, the iliac vessels, the trachea, the esophagus, etc.), or the risk of
developing a tracheo-esophageal fistula or an esophago-pleural fistula.
10. Uncontrollable hypertension, with a systolic blood pressure of =150mmHg or a diastolic
blood pressure of =100mmHg, history of hypertension crisis or hypertension cerebral
infarction.
11. Symptomatic congestive heart failure (New York Heart Association classification
II-IV). Symptomatic or uncontrolled arrhythmia. QT interval prolongation, QTcF>470ms.
12. Severe bleeding tendency or coagulation disorder, or currently receiving thrombolytic
therapy.
13. History of gastrointestinal perforation and/or fistula within the past 6 months,
history of bowel obstruction (including incomplete bowel obstruction requiring
parenteral nutrition), inflammatory bowel disease or extensive bowel resection
(partial colon resection or extensive small bowel resection with chronic diarrhea),
Crohn's disease, ulcerative colitis, or chronic diarrhea.
14. History of interstitial pneumonitis, drug-induced pneumonitis, radiation pneumonitis,
idiopathic pneumonitis, or active pneumonitis. 15) Active tuberculosis (TB), who are
currently receiving anti-TB treatment or have received anti-TB treatment within 1 year
prior to the start of the study.
16) Individuals with Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibody
positive), known active syphilis infection.
17) Severe infections that are active or not well controlled. A severe infection within 4
weeks prior to the first dose, including but not limited to hospitalization due to
infection, sepsis, or severe pneumonia complications.
18) Oral or intravenous administration of therapeutic antibiotics within 1 week prior to
the start of the study.
19) Active systemic autoimmune diseases or a history of such disease within the past 2
years (Psoriasis, alopecia, vitiligo, or Graves' disease that do not require systemic
treatment within the past 2 years, hypothyroidism that only requires thyroid hormone
replacement therapy, and type 1 diabetes that only requires insulin replacement therapy can
be included). A history of primary immunodeficiency is known. Only individuals with
positive autoimmune antibodies need to be confirmed by the investigator for the presence of
autoimmune diseases. 20) You have used an immunosuppressive drug within the past 4 weeks,
excluding topical or inhaled corticosteroids or physiological doses of systemic
corticosteroids (i.e., no more than 10 mg of prednisone or equivalent daily doses of other
corticosteroids) used for the relief of breathing difficulties associated with conditions
such as asthma or chronic obstructive pulmonary disease.
21) You have received a live attenuated vaccine within the past 4 weeks or plan to receive
one during the study.
22) You have received systemic immune stimulation therapy within the past 4 weeks.
23) You have had a major surgical procedure (craniotomy, thoracotomy, or laparotomy) within
the past 4 weeks or have an unhealed wound, ulcer, or fracture.
24) You have an uncontrolled/uncorrectable metabolic disorder or other non-malignant tumor
organ disease or systemic disease or cancer-related complications that may result in higher
medical risk and/or uncertainty in survival assessment.
25) You have any other acute or chronic disease, mental illness, or laboratory test
abnormality that may increase the risk of participating in the study or receiving study
medication, or interfere with the interpretation of study results, as determined by the
investigator.
26) You have previously received nintedanib or other anti-EGFR therapy. 27) You have
previously received sunitinib therapy. 28) Previous treatment with anti-CTLA-4 antibody.
29) Known to be allergic to any nivolumab, siltuximab component; or had a severe allergic
reaction to other monoclonal antibodies in the past.
30) Received any anti-cancer treatment within 4 weeks prior to starting the study: systemic
chemotherapy (oral fluoropyrimidine washout period is 2 weeks), endocrine therapy, targeted
therapy (small molecule targeted therapy washout period is 2 weeks or 5.5 half-lives,
whichever is longer), immunotherapy, tumor embolization therapy, or traditional Chinese
medicine treatment for anti-cancer indications, etc.
31)Pregnant or breastfeeding female patients.
|
