Induction Chemotherapy Plus Cadonilimab for Locally Advanced Cervical Cancer

NCT06511726 | Active Not Recruiting Phase 2

• 1 other identifier: SYSKY-2023-1101-04
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated, single-arm, phase II clinical study evaluating the efficacy and safety of cadonilimab combined with induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced cervical cancer (LACC). Despite standard concurrent chemoradiotherapy, patients with LACC remain at high risk of recurrence and distant metastasis. Cadonilimab, a PD-1/CTLA-4 bispecific antibody, has demonstrated promising antitumor activity in cervical cancer. This study aims to investigate whether induction immunochemotherapy with cadonilimab combined with cisplatin and albumin-bound paclitaxel can improve tumor response before definitive radiotherapy. In addition, the study will explore the association between treatment efficacy and dynamic changes in PD-L1 expression, peripheral blood immune-related biomarkers, and tumor microenvironment immune cell populations during treatment. The primary endpoint is objective response rate (ORR) assessed according to RECIST version 1.1, while secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Conditions

Cervical Cancer

Keywords

cervical cancer; immunotherapy; Induction chemotherapy; Cadonilimab

Outcome Measures

Primary Outcomes (1)

• ORR

  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.

  up to18 months

Secondary Outcomes (4)

• OS

  up to approximately 46 months

• PFS

  up to approximately 46 months

• DCR

  up to approximately 46 months

• Incidence of treatment-related adverse events (TRAEs)

  From initiation of induction therapy to 90 days after completion of radiotherapy

Study Arms (1)

Cadonilimab plus induction chemotherapy followed by CCRT

EXPERIMENTAL

Patients will receive induction immunochemotherapy consisting of cadonilimab combined with cisplatin and albumin-bound paclitaxel for 2 cycles, followed by concurrent chemoradiotherapy (CCRT). During CCRT, cisplatin will be administered weekly concurrently with external beam radiotherapy and brachytherapy.

Drug: Cadonilimab; Drug: Cisplatin; Drug: Albumin-Bound Paclitaxel /nab-Paclitaxel; Radiation: Concurrent chemoradiotherapy

Interventions

Cadonilimab DRUG

Cadonilimab will be administered intravenously in combination with cisplatin and albumin-bound paclitaxel as induction immunochemotherapy for 2 cycles.

Cadonilimab plus induction chemotherapy followed by CCRT

Cisplatin DRUG

Cisplatin will be administered during induction chemotherapy and weekly during concurrent chemoradiotherapy.

Cadonilimab plus induction chemotherapy followed by CCRT

Albumin-Bound Paclitaxel /nab-Paclitaxel DRUG

Albumin-bound paclitaxel will be administered intravenously in combination with cadonilimab and cisplatin during induction therapy.

Cadonilimab plus induction chemotherapy followed by CCRT

Concurrent chemoradiotherapy RADIATION

External beam radiotherapy will be delivered using 6-MV X-rays at a total dose of 45-60 Gy in 25 fractions, followed by brachytherapy at a dose of 30 Gy in 5 fractions. Weekly cisplatin (30-40 mg/m²) will be administered concurrently during radiotherapy.

Cadonilimab plus induction chemotherapy followed by CCRT

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-2.
• Main organ functions meet the protocol criteria within 7 days before treatment.

You may not qualify if:

• 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).
• Within 4 weeks, experienced severe infections, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia.
• Within 4 weeks, underwent major surgical treatment (as determined by the investigator), open biopsy, or significant trauma or requires scheduled major surgical treatment during the study. Diagnostic systematic pelvic/aortic lymphadenectomy is allowed.
• Received live vaccines within 4 weeks .
• With active or history of documented autoimmune diseases exceptions include: vitiligo, alopecia, psoriasis, or eczema that do not require systemic treatment hypothyroidism caused by autoimmune thyroiditis requiring stable dose of hormone replacement therapy type 1 diabetes requiring stable dose of insulin replacement therapy.
• Any of the following cardiovascular diseases: a) New York Heart Association (NYHA) functional classification ≥ II for heart failure. b) Presence of severe arrhythmias requiring long-term drug intervention asymptomatic patients with stable ventricular rate in atrial fibrillation are allowed to enroll. c) Occurrence of cerebrovascular events (CVA) within 6 months . d) Left ventricular ejection fraction (LVEF) \< 50%.
• Known primary or secondary immunodeficiency, including positive human immunodeficiency virus (HIV) antibody test.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-sen Memorial hosipital

Guangzhou, Guangdong, 510000, China

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Cisplatin; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Shoumin Bai

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 22, 2024
• Study Start: January 23, 2024
• Primary Completion: November 20, 2024
• Study Completion (Estimated): April 30, 2029
• Last Updated: June 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)