Cervical cancer
Conditions
Interventions
Trial group (Simon two-stage design, Phase 1):1. Neoadjuvant period:
Disitamab Vedotin (2.5 mg/kg, D1, iv, Q3W
three cycles in total)
Cisplatin (50 mg/m^2, D1, iv, Q3W
three cycles in total)
Cadonilimab (10 mg/kg, D1, iv, Q3W
three cycles in total)
2. Surgery period:
For patients who achieve CR/PR/SD after neoadjuvant therapy, extensive total hysterectomy + bilateral adnexectomy + pelvic lymph node dissection +/- para
maintenance treatment for half a year)
Trial group (Simon two-stage design, Phase 2):1. Neoadjuvant period:
Disitamab Vedotin (2.5 mg/kg, D1, iv, Q3W
Sponsors
Dalian Medical University Second Affiliated Hospital
Eligibility
Sex/Gender
Female
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Voluntarily agree to participate in the research and sign the informed consent form; 2. Age: 18-75 years old; 3. Expected survival period>=12 weeks; 4.ECOG PS 0-1; 5. Patients with locally advanced cervical cancer (including IB3 and IIA2 stages) who have not received systematic treatment in the past and those with pelvic lymph node metastasis on imaging (IIIC1 stage); 6. It has measurable lesions as stipulated in the RECIST v1.1 standard; 7. Our laboratory confirmed the expression status of PD-L1 and HER2, with HER2 requiring IHC > 0. The subjects can provide specimens of the primary or metastatic tumor sites for HER2 detection (paraffin blocks, paraffin-embedded sections or fresh tissue sections are all acceptable), and HER2 IHC interpretation will be conducted in accordance with the interpretation standards of gastric cancer in 2016. 8. Sufficient organ function: (1) Bone marrow function: Hemoglobin>=9g/dL; Absolute neutrophil count >=1.5×10^9/L; White blood cell count >=3.0×10^9/L; Platelet count >=100×10^9/L; (2).Liver function: Serum total bilirubin =60 mL/min; (4).Cardiac function: New York College of Cardiology (NYHA) grade =50%; 9. Women of childbearing age must have taken reliable contraceptive measures or undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and be willing to undergo the test; 10. The subjects voluntarily joined this study, signed the informed consent form, had good compliance and cooperated with the follow-up.
Exclusion criteria
Exclusion criteria: 1. Previously received ADC drugs, immunotherapy drugs, anti-HER2 treatment, etc. 2. Subjects with a history of other malignant tumors within five years (excluding complete treatment of cervical cancer in situ, basal cell carcinoma, squamous cell carcinoma or skin cancer); 3. Severe cardiovascular and cerebrovascular diseases or discomforts, including but not limited to the following diseases: (1).a confirmed history of heart failure or systolic dysfunction (LVEF 180 mmHg and/or diastolic blood pressure > 100 mmHg; 4. Those who have a history of allergy to the drug components of this plan; 5. Use immunosuppressive drugs or systemic corticosteroids for immunosuppression (prednisone or other equivalent drugs 100 mg per day) within 2 weeks before the trial administration; Permitted for external use, such as intraocular, intra-articular, intranasal and inhaled corticosteroids; 6. Severe infection occurs within 4 weeks before the first medication (e.g., requiring intravenous infusion of antibiotics, antifungal or antiviral drugs); 7. Take herbal medicines with anti-tumor effects or drugs with immunomodulatory effects (such as thymidine, interferon, interleukin-2) within two weeks before the trial; 8. Those with active autoimmune diseases, immune deficiencies, organ transplants, or a history of the above (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, rheumatoid arthritis, inflammatory bowel disease, pituitinitis, vasculitis, nephritis, etc.) are not eligible for inclusion. The following exceptions apply: Patients with a history of autoimmune hypothyroidism but who have received thyroid hormone replacement therapy can be included in the study. Patients with type 1 diabetes whose blood sugar was controlled after treatment with insulin administration regimens can participate in this study. 9. Severe infections that are in the active stage or have poor clinical control; Active infections, including: (1).Positive for the Human immunodeficiency virus (HIV) (HIV-1/2 antibody); (2).Active hepatitis b (HBsAg positive or HBV DNA > 2000IU/ml with abnormal liver function); (3).Active hepatitis c (positive HCV antibody or HCV RNA=103 copies /ml with abnormal liver function); (4).Active tuberculosis; (5).Other uncontrollable active infections (CTCAE V5.0 > grade 2); 10. Pregnant and lactating female patients, female patients with fertility and positive baseline pregnancy test results, or patients of childbearing age who are unwilling to take effective contraceptive measures throughout the trial period; 11.The patient has serious concomitant diseases or other comorbidities that may interfere with the planned treatment, or any other circumstances that the researcher deems unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathologic complete response, PCR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Event-free survival, EFS;Objective response rate,ORR;Disease Control Rate,DCR;margin-free (R0) resection rate;Major Pathological response,MPR;Safety; | — |
Countries
China
Contacts
Public ContactWang Ning
Dalian Medical University Second Affiliated Hospital
Outcome results
None listed