Induction Chemotherapy Plus Cadonilimab Followed by Chemoradiotherapy for Locally Advanced Cervical Cancer: A Multicenter, Open-label, Single-arm, Phase II Trial
Overview
- Phase
- Phase 2
- Intervention
- Cadonilimab
- Conditions
- Cervical Cancer
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- ORR
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a Phase II clinical study for patients with locally advanced cervical cancer, aimed at evaluating the efficacy, safety, and tolerability of Cadonilimab combined with chemotherapy as induction therapy.
Detailed Description
This is a Phase II clinical study for patients with locally advanced cervical cancer, aimed at evaluating the efficacy, safety, and tolerability of Cadonilimab combined with chemotherapy induction therapy, as well as exploring the correlation between the expression level of PD-L1 in tumor samples, changes in blood and tumor-local immune-related factors and cells during treatment, and the efficacy of Cadonilimab induction therapy. The study is divided into two stages, with the first stage requiring the enrollment of 9 patients. If the number of effective cases is ≤7, the trial will be terminated; if \>7 cases, it will proceed to the second stage, continuing to enroll patients until reaching 29. The Cadonilimab dosing regimen involves immunotherapy combined with chemotherapy induction, Cadonilimab and cisplatin and albumin-bound paclitaxel, for a total of 2 cycles. The radiotherapy and chemotherapy regimen includes cisplatin 30-40 mg/m2, once weekly for 5 times, external radiation (6MV-X-ray) at a dose of 45-60Gy/25F; and brachytherapy at a dose of 30Gy/5F. The primary endpoint of the study is ORR, with secondary endpoints being OS, PFS, and DCR.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with good compliance.
- •Age ≥ 18 years (calculated on the day of signing the informed consent).
- •Histologically or pathologically diagnosed with cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma) and measurable lesions.
- •Initial diagnosis of stage IB3-IVA (according to FIGO 2018 staging).
- •ECOG performance score of 0-
- •Main organ functions meet the protocol criteria within 7 days before treatment.
Exclusion Criteria
- •Patients with other histological types of cervical cancer, such as neuroendocrine carcinoma or sarcoma.
- •Evidence of distant metastasis, including groin lymph node metastasis and lymph node metastasis above the L1 level.
- •Previously underwent total hysterectomy (removal of the uterus body + cervix). History of subtotal hysterectomy or cervical wedge resection that preserves the cervix is allowed.
- •With anatomical abnormalities or tumor geometry-related contraindications that prevent the use of brachytherapy.
- •Within 2 years, had other active malignant tumors, except for locally curable tumors that have been cured, such as squamous cell carcinoma of the skin, basal cell carcinoma of the skin, superficial bladder cancer, and ductal carcinoma in situ of the breast.
- •With clinically significant bilateral hydronephrosis that, in the investigator's judgment, cannot be relieved by nephrostomy or ureteral stent placement.
- •Previously received immune checkpoint inhibitors (e.g., anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies) or any treatment targeting tumor immune mechanisms involving immune co-stimulatory factors (e.g., antibodies targeting ICOS, CD40, CD137, GITR, OX40).
- •Within 2 weeks, requires the use of glucocorticoids (\> 10 mg/day prednisone or equivalent dose of glucocorticoids) or other immunosuppressive drugs for systemic treatment exceptions include: a) Allowed treatment with inhaled, ophthalmic, or local doses ≤ 10 mg/day prednisone or equivalent dose of glucocorticoids. b) Physiological glucocorticoid replacement therapy at a dose ≤ 10 mg/day prednisone or equivalent dose of glucocorticoids. c) Glucocorticoids used for prophylaxis against hypersensitivity reactions (e.g., premedication for CT scans).
- •Within 2 weeks, received drugs with immunomodulatory effects (e.g., thymosin, interferon, interleukin-2).
- •Presence of active systemic infections requiring systemic treatment (including active pulmonary tuberculosis, active syphilis caused by Treponema pallidum, and fungal infections requiring systemic treatment) note: exclusion does not apply to antiviral drugs used for hepatitis B virus infection.
Arms & Interventions
Cadonilimab plus Cisplatin and Albumin-Bound Paclitaxel as Induction therapy Followed by CCRT
This is a single-arm study. The experimental arm includes Cadonilimab + cisplatin + albumin-bound paclitaxel, for a total of 2 cycles (cisplatin 75 mg/m² + albumin-bound paclitaxel 260 mg/m² q3w, Cadonilimab 10 mg/kg q3w).
Intervention: Cadonilimab
Outcomes
Primary Outcomes
ORR
Time Frame: up to18 months
At 2 weeks post-induction therapy, objective response rate represents the proportion of patients showing a predefined level of tumor shrinkage or disappearance in response to treatment.
Secondary Outcomes
- OS(up to approximately 46 months)
- PFS(up to approximately 46 months)
- DCR(up to approximately 46 months)