Locally Advanced Cervical Cancer
Conditions
Keywords
Locally advanced cervical cancer, Adebrelimab, Neoadjuvant therapy, Pathologic complete response, Circulating tumor human papillomavirus DNA, Minimal residual disease
Brief summary
This prospective, single-center, single-arm, phase II study will evaluate perioperative adebrelimab in patients with locally advanced cervical cancer. Approximately 35 participants will receive three 3-week cycles of neoadjuvant adebrelimab in combination with paclitaxel and cisplatin or carboplatin. Participants without disease progression who are considered resectable will undergo radical hysterectomy and pelvic lymph node dissection 28-42 days after the last cycle of neoadjuvant treatment. Postoperative treatment will be risk-adapted according to pathological risk factors. Participants with high-risk pathological factors will discontinue protocol treatment and receive standard concurrent chemoradiotherapy. Participants with intermediate-risk factors will receive guideline-recommended pelvic radiotherapy plus adebrelimab maintenance, whereas low-risk participants will receive adebrelimab maintenance. Adebrelimab maintenance will be administered every 3 weeks for up to 1 year and may be discontinued early after two consecutive negative circulating tumor HPV DNA tests at least 3 months apart. The primary endpoint is the pathologic complete response rate. Secondary endpoints include objective response rate, disease control rate, disease-free survival, 2-year disease-free survival rate, overall survival, duration of response, quality of life, and safety. Dynamic circulating tumor HPV DNA will also be explored as a biomarker of treatment response and postoperative recurrence risk.
Interventions
DRUGAdebrelimab
debrelimab 1200 mg will be administered intravenously every 3 weeks for three cycles during neoadjuvant treatment. Eligible participants will subsequently receive postoperative adebrelimab maintenance at 1200 mg intravenously every 3 weeks for up to 1 year, or until protocol-defined discontinuation criteria are met.
DRUGPaclitaxel
Paclitaxel 175 mg/m² will be administered intravenously every 3 weeks for three cycles as part of neoadjuvant treatment.
DRUGCisplatin
Cisplatin 70-75 mg/m² will be administered intravenously every 3 weeks for three cycles as a platinum option during neoadjuvant treatment.
Carboplatin AUC 5 will be administered intravenously every 3 weeks for three cycles as an alternative platinum option during neoadjuvant treatment.
Sponsors
Anhui Provincial Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants will receive three cycles of neoadjuvant adebrelimab plus paclitaxel and cisplatin or carboplatin every 3 weeks. Participants considered resectable after neoadjuvant treatment will undergo radical hysterectomy and pelvic lymph node dissection 28-42 days after the last neoadjuvant cycle. Postoperative treatment will be determined by pathological risk factors. High-risk participants will discontinue protocol treatment and receive standard concurrent chemoradiotherapy; intermediate-risk participants will receive pelvic radiotherapy plus adebrelimab maintenance; and low-risk participants will receive adebrelimab maintenance. Maintenance adebrelimab will continue every 3 weeks for up to 1 year and may be stopped early after two consecutive negative ctHPV DNA tests at least 3 months apart.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18 to 75 years. * Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix; FIGO 2018 stage IB3 or IIA2, or carefully selected stage IIB or IIIC1r disease following multidisciplinary team evaluation, with a maximum primary tumor diameter ≥4 cm. For participants with stage IIB or IIIC1r disease, PET/CT or an equivalent staging examination must exclude para-aortic lymph node metastasis and distant metastasis, and definitive concurrent chemoradiotherapy must remain feasible if neoadjuvant treatment is ineffective. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Able to provide adequate tumor tissue for biomarker testing, defined as at least 18 qualified tissue sections. * No prior surgery for cervical cancer, except staging procedures, and no prior radiotherapy, chemotherapy, systemic anticancer therapy, investigational therapy, or immunotherapy for cervical cancer. * At least one measurable lesion according to RECIST version 1.1, defined as a tumor lesion with a longest diameter ≥10 mm on CT or a lymph node with a short-axis diameter ≥15 mm on CT. * Estimated life expectancy ≥6 months. * No primary or metastatic central nervous system disease. * Adequate major organ function, meeting all of the following criteria: * No blood or blood-product transfusion within 14 days before assessment; * Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; * Platelet count ≥80 × 10⁹/L; * Hemoglobin ≥9 g/dL; * Total bilirubin \<1.5 × upper limit of normal (ULN); * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN; * Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula. * Positive for high-risk human papillomavirus (HPV) DNA. * Written informed consent provided and willingness to comply with protocol-required follow-up.
Exclusion criteria
* Considered unsuitable for participation in the study by the investigator. * Known hypersensitivity or allergy to any study drug. * Any active, known, or suspected autoimmune disease, including but not limited to interstitial pneumonitis, uveitis, enteritis, hepatitis, arthritis, nephritis, hypophysitis, hyperthyroidism, or hypothyroidism; vitiligo; or asthma requiring medical intervention with bronchodilators. * Congenital or acquired immunodeficiency, including HIV infection, hepatitis B, or hepatitis C. * Prior treatment with PD-1 and/or PD-L1 inhibitors, CTLA-4 antibodies, or other agents targeting immune-regulatory receptors. * Current use of immunosuppressive agents. Patients in a stable condition who do not require systemic immunosuppressive therapy may be eligible. * Long-standing unhealed wounds or fractures; major surgery, severe traumatic injury, fracture, or ulcer within 4 weeks before initiation of study treatment. * Poorly controlled cardiac symptoms or cardiovascular disease, including New York Heart Association (NYHA) class III-IV heart failure or left ventricular ejection fraction (LVEF) \<50%; abnormal coagulation function defined as INR \>1.5 or APTT \>1.5 × ULN with a bleeding tendency; or an arterial or venous thromboembolic event within 6 months before the first dose of study treatment. * Symptomatic ascites, pleural effusion, or pericardial effusion requiring therapeutic puncture or drainage. Patients whose pleural or pericardial effusion remains stable for at least 2 weeks after drainage before the first dose of study treatment may be eligible. * Central nervous system metastases. * History of another malignancy, except for cured basal cell carcinoma of the skin or cervical carcinoma in situ. * Pregnant or breastfeeding women. * History of psychotropic drug abuse with inability to discontinue such use, or presence of a psychiatric disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) Rate | At definitive surgery, planned 28-42 days after completion of the third cycle of neoadjuvant treatment (approximately 10-12 weeks after initiation of treatment) | The proportion of participants achieving pathologic complete response following neoadjuvant treatment. pCR is defined as no residual invasive carcinoma in the cervical primary tumor and no metastatic carcinoma in any resected regional lymph node, with ypT0/is ypN0 used as the operational definition. The primary analysis denominator will include all participants who receive at least one dose of study treatment. Participants who do not undergo surgery, experience disease progression, withdraw, die, or have missing primary endpoint data will be considered not to have achieved pCR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From baseline to preoperative tumor assessment after completion of three cycles of neoadjuvant treatment, approximately 9 weeks | Proportion of participants achieving complete response or partial response according to RECIST version 1.1. |
| Disease Control Rate (DCR) | From baseline to preoperative tumor assessment after completion of three cycles of neoadjuvant treatment, approximately 9 weeks | Proportion of participants achieving complete response, partial response, or stable disease according to RECIST version 1.1. |
| Disease-Free Survival (DFS) | From definitive surgery to disease recurrence, death, or last disease-free follow-up, assessed through December 31, 2029 | Time from definitive surgery to the first documented disease recurrence or death from any cause, whichever occurs first. Participants without an event will be censored at the date of the last known disease-free assessment. |
| Two-Year Disease-Free Survival Rate | 2 years after definitive surgery | Proportion of participants alive and free of disease recurrence 2 years after definitive surgery. |
| Overall Survival (OS) | From first study treatment to death or last known alive, assessed through December 31, 2029 | Time from the first administration of study treatment to death from any cause. Participants alive at the time of analysis will be censored at the date last known alive. |
| Duration of Response (DOR) | From first documented CR or PR to disease progression or death, assessed through December 31, 2029 | Among participants who achieve a complete or partial response, duration from the first documented response to disease progression or death before progression. |
| Incidence of Adverse Events | From the first dose of study treatment through 90 days after the last dose or initiation of a new anticancer treatment, whichever occurs first | Incidence and severity of adverse events, treatment-emergent adverse events, and serious adverse events, graded according to NCI CTCAE version 5.0. |
| ORTC QLQ-C30 Scores Outcome | Baseline and at the end of each 21-day treatment cycle during study treatment, through completion of study treatment, up to 1 year | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) is a 30-item questionnaire used to assess health-related quality of life in patients with cancer. Scores for each scale are linearly transformed to a range from 0 to 100. Higher scores on the functional scales and the global health status/quality-of-life scale indicate better functioning or quality of life, whereas higher scores on the symptom scales and single symptom items indicate greater symptom severity or problems. Change from baseline in EORTC QLQ-C30 scores will be assessed during study treatment. |
| EORTC QLQ-CX24 Outcome | Baseline and at the end of each 21-day treatment cycle during study treatment, through completion of study treatment, up to 1 year | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module 24 (EORTC QLQ-CX24) Scores. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module 24 (EORTC QLQ-CX24) is a 24-item cervical cancer-specific quality-of-life questionnaire used in conjunction with the EORTC QLQ-C30. It assesses symptom experience, body image, sexual/vaginal functioning, lymphedema, peripheral neuropathy, menopausal symptoms, sexual worry, sexual activity, and sexual enjoyment. All scale and single-item scores are linearly transformed to a range from 0 to 100. Higher scores on symptom scales/items indicate greater symptom severity or problems, whereas higher scores for the functional items of sexual activity and sexual enjoyment indicate better functioning. Change from baseline in EORTC QLQ-CX24 scores will be assessed during study treatment. |
Countries
China
Contacts
CONTACTYing Zhou
Outcome results
None listed