Advanced cervical cancer
Conditions
Interventions
Subjects who do require induction chemotherapy:Adebrelimab injection/placebo administration
radiotherapy
paclitaxel
Subjects who do not require induction chemotherapy:Adebrelimab injection/placebo + cisplatin/carboplatin + radiotherapy
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
Female
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Subjects voluntarily participate in this study, having signed the informed consent form, demonstrate good compliance, and are able to cooperate with follow-up visits. 2.Female, aged 18–75 years (inclusive, calculated at the date of informed-consent signature). 3.Patients must have histopathological confirmation of cervical squamous-cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. 4.Clinical stage III–IVA (FIGO 2018). For stage IIIC1 all of the following must be present: MRI or CT shows =2 positive pelvic lymph nodes with short-axis =1.5 cm, and Primary tumour longest diameter >4 cm. Stage IIIC2 para-aortic nodal involvement is established if any one of the following applies: Histologically proven positive node(s) on biopsy; MRI or CT shows =1 positive para-aortic node with short-axis =1.5 cm; PET/CT shows =1 positive para-aortic node with SUVmax =2.5. Induction therapy is mandatory when either: Primary tumour longest diameter >6 cm, or Any lymph-node short-axis =3 cm. 5.At least one measurable lesion per RECIST 1.1 must be present (longest diameter =10 mm on MRI or CT for non-nodal lesions, or short-axis =15 mm for pathologic lymph nodes). 6.Judged by the investigator to be suitable for concurrent chemoradiotherapy for cervical cancer. 7.ECOG performance status 0–1; 8.BMI = 18.5 kg/m²; 9.Capable of providing archival tumour tissue (formalin-fixed, paraffin-embedded [FFPE] tissue block or unstained FFPE slides) or willing to undergo a biopsy during screening to supply fresh tumour tissue. 10.Expected survival > 3 months; 11.Adequate organ and bone-marrow function as follows (all tests within 14 days before randomisation, without transfusions, G-CSF, or other corrective therapy): 1) Haematology - Haemoglobin =90 g/L - Absolute neutrophil count =1.5 × 10?/L - Platelet count =100 × 10?/L - White-cell count =3.0 × 10?/L and <15 × 10?/L 2) Biochemistry & other assays (no IV albumin within 14 days) - AST and ALT =3 × ULN - ALP =2.5 × ULN (=5 × ULN if bone metastases) - Total bilirubin =1.5 × ULN - Albumin =30 g/L - Creatinine clearance =60 mL/min (Cockcroft-Gault) - TSH =1 × ULN (if abnormal, FT3 and FT4 must be normal) - APTT =1.5 × ULN and PT =1.5 × ULN or INR <1.5 (<3 if on anticoagulation) - QTcF <470 ms; left-ventricular ejection fraction =50 %; 12.Women of childbearing potential must agree to use a highly effective contraceptive method during the study-treatment period and for 7 months after the last dose, and must refrain from donating oocytes. A serum pregnancy test (ß-hCG) obtained within 3 days before enrolment must be negative (a positive result may be disregarded if the investigator judges it clinically insignificant and pregnancy is ruled out). Breast-feeding is not permitted.
Exclusion criteria
Exclusion criteria: 1.Histopathologically confirmed small-cell (neuroendocrine) cervical carcinoma, mucinous adenocarcinoma, or any other rare histological subtype. 2.Pathologically or radiologically documented distant metastatic disease, including lymph nodes above the first lumbar vertebra (L1) (cranial side) or in the inguinal region. 3.Current or history of bladder, vaginal, or rectal fistula; OR imaging showing tumour invasion of the bladder or rectum that, in the investigator’s judgement, carries a risk of perforation. 4.Previous hysterectomy (including sub-total hysterectomy) or planned hysterectomy for cervical cancer, or intention to use fertility-sparing treatment. 5.Prior or ongoing treatment with any of the following is excluded: 1) Surgery (except biopsy, puncture, or palliative local surgery =1 week before enrolment), chemotherapy, radiotherapy, or molecular-targeted therapy (including oral targeted drugs from other trials) for cervical cancer. 2) Any immunotherapy, including but not limited to anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies, bispecific antibodies, or therapeutic cancer vaccines. 3) Live-vaccine administration within 4 weeks before enrolment or planned during the study. 4) Immunosuppressive therapy within 4 weeks before enrolment, except topical steroids, systemic corticosteroids =10 mg/day prednisone (or equivalent), or prophylactic use for hypersensitivity reactions. 6.Bilateral hydronephrosis unless already relieved by stenting or nephrostomy; unilateral hydronephrosis with normal renal function is permitted. 7.Patients receiving thrombolytic/anticoagulant therapy are excluded, except for those on prophylactic anticoagulation. 8.Other malignancies that have not been cured within the past 5 years are excluded, with the exception of cured basal cell carcinoma of the skin and carcinoma in situ. 9.Patients with any active or known autoimmune disease are excluded (including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, colitis, multiple sclerosis, vasculitis, glomerulonephritis, uveitis, hypophysitis, hyperthyroidism, etc.). However, the following conditions are allowed: - Type 1 diabetes mellitus on stable insulin therapy - Hypothyroidism on stable hormone replacement therapy - Hashimoto's thyroiditis not requiring treatment - Skin disorders (e.g., eczema, vitiligo, psoriasis) not requiring systemic therapy and without acute exacerbation within 1 year before screening; 10.History of interstitial lung disease (ILD) or current non-infectious pulmonary inflammation requiring corticosteroid treatment. 11.Severe infection within 4 weeks before enrolment requiring IV antibiotics, antifungals, or antivirals; OR fever >38.5 °C of unknown cause within 7 days before enrolment; OR active pulmonary tuberculosis (patients cured after adequate anti-TB therapy stopped =3 months before enrolment are eligible). 12.Congenital or acquired immunodeficiency (e.g., HIV infection); active hepatitis defined as: - HBsAg-positive with HBV DNA = 500 IU/mL (or = 1,000 copies/mL), or - anti-HCV-positive with HCV RNA > ULN; or history of allogeneic organ transplantation. 13.Known hereditary or acquired bleeding or thrombotic diathesis (e.g., haemophilia, coagulation disorders). 14.Arterial or venous thrombo-embolic events within 6 months before enrolment, including cerebrovascular accident (TIA, intracranial haemorrhage, cerebral infarction), deep-ve
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| progression-free survival;Overall Survival; | — |
Countries
China
Contacts
Public ContactXiaohua Wu
Fudan University Shanghai Cancer Center
Outcome results
None listed