Prospective registration

Sequential Cisplatin/Paclitaxel and Tislelizumab as neoadjuvant therapy for locally advanced cervical cancer: an open-label, single-center, single-arm phase II trial

Sequential Cisplatin/Paclitaxel and Tislelizumab as neoadjuvant therapy for locally advanced cervical cancer: a single-arm phase II trial

Sequential Cisplatin/Paclitaxel and Tislelizumab as neoadjuvant therapy for locally advanced cervical cancer: an open-label, single-center, single-arm phase II trial

Xiaohong Ruan 

Xiaohong Ruan 

Haibang Road 23, North Street, Pengjiang District, Jiangmen City, GuangDong Province.

Haibang Road 23, North Street, Pengjiang District, Jiangmen City, GuangDong Province.

Jiangmen Central Hospital

Jiangmen Central Hospital

Yes

Clinical Trial Ethics Committee of Jiangmen Central Hospital

Linsheng Guo

Haibang Road 23, North Street, Pengjiang District, Jiangmen City, GuangDong Province.

Jiangmen Central Hospital

Haibang Road 23, North Street, Pengjiang District, Jiangmen City, GuangDong Province.

NA

cervical cancer

Interventional study

2

Single arm 

To evaluate the efficacy and safety of Cisplatin/Paclitaxel sequential Tislelizumab as neoadjuvant therapy for locally advanced cervical cancer

1. The clinical diagnosis cervical cancer according to FIGO 2018 stages are IB3, IIA2 and IIIC1r with local tumour maximum diameter ≥4cm. 2. Histopathologically confirmed cervical squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma. 3. Ages 18-70 year. 4. ECOG 0-1 and expected survival ≥6 months. 5.WBC≥3.5×109/L,Hb≥100g/L,PLT≥90×109/L when routine analysis of blood. Cardiac and liver function well(TBil≤1.5ULN, ALT≤2.5ULN, AST≤2.5ULN), kidney funtion well(serum Cr≤1.5ULN) ,coagulation function well. 6. No other antitumor concomitant therapy (including steroid drugs) 7. No other serious diseases conflict with this study 8. Without previous surgery, radiation or systemic treatment for cervical cancer 9. Agree with chemotherapy and related therapy. Sign informed consent for this clinical trial.

1. Previous immunotherapy, including immune checkpoint inhibitory antibodies (such as anti-PD-1, PD-L1, CTLA-4 antibodies, etc.), immune checkpoint agonist antibodies (such as anti-ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), and immune cell therapy; Prior receipt of VEGF/VEGFR inhibitors such as bevacizumab, ramucirumab, aflibercept, and tyrosine kinase inhibitors. 2. Systemic infection or other serious infection requiring intravenous antibiotics > 7 days of treatment within 2 weeks prior to enrollment, or fever of unknown cause > 38.5 degrees during the screening period and before enrollment (except for fever caused by tumor in the judgment of the investigator). 3. Presence of disease requiring systemic use of corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive drugs (such as cyclophosphamide, azathioprine, methotrexate, thalidomide, TNF-α inhibitors, etc.) within 2 weeks prior to enrollment. Topical corticosteroids, nasal sprays, and inhaled steroids are allowed. Systemic corticosteroids are allowed for the prevention of contrast allergy. 4. Received systemic therapy with immunomodulatory drugs (such as thymopeptide, lentinan polysaccharide, interferon, interleukin, etc.) within 2 weeks prior to enrollment. 5. Treatment with aspirin (> 325 mg/day), clopidogrel (> 75 mg/day), dipyridamole, ticlopidine, and cilostazol within 2 weeks prior to enrollment and the use of other anticoagulant therapy for therapeutic purposes (except for low molecular weight heparin therapy). 6. Within 2 weeks prior to enrollment, have received modern traditional Chinese medicine preparations approved by NMPA for anti-tumor treatment. 7. Major surgical treatment, open biopsy or significant trauma within 4 weeks prior to enrollment; or requires elective major surgical treatment during the study. Received local invasive procedures (such as needle core biopsy) within 1 week prior to enrollment, except for the placement of vascular access devices. 8. Received anti-tumor therapy, such as chemotherapy, endocrine therapy, targeted therapy, biological therapy, tumor embolization, etc., within 4 weeks before enrollment. 9. Presence of symptomatic central nervous system (CNS) metastases, leptomeningeal metastases, or spinal cord compression due to metastases prior to signing informed consent. Patients who are asymptomatic and have clinical and/or radiographic evidence that their condition is stable, who have stopped treatment with corticosteroids and anticonvulsants for at least 2 weeks, and who do not require further treatment (radiotherapy, surgical resection, and/or corticosteroid therapy) may participate in this study. 10. Currently have clinically significant hydronephrosis, which cannot be relieved by nephrostomy or ureteral stenting as judged by the investigator. 11. At present, there is a third space effusion with poor clinical control and requires repeated puncture and drainage. 12. Have an active or potentially recurrent autoimmune disease, with the following exceptions: vitiligo, alopecia, psoriasis, or eczema not requiring systemic treatment; Hypothyroidism due to autoimmune thyroiditis requiring only stable doses of hormone replacement therapy; Type I diabetes requiring only stable doses of insulin replacement therapy. 13. History of gastrointestinal perforation or fistula, genitourinary fistula, intra-abdominal abscess within 6 months prior to enrollment, and it is acceptable if the underlying factors leading to perforation or fistula have been corrected by surgery. 14. History of intestinal obstruction within 6 months prior to enrollment (if the subject with symptoms and signs of incomplete obstruction/obstruction has been treated and the symptoms have subsided at the time of initial diagnosis, he can be enrolled after evaluation by the investigator), active inflammation in the abdomen (including but not limited to peptic ulcer, diverticulitis or colitis). 15 Subjects with any of the following cardiovascular diseases: (3 sub-strips) a) Myocardial infarction, unstable angina, pulmonary embolism, or other clinically significant/requiring pharmacological intervention of arteriovenous thrombosis, embolism, or cerebrovascular events within 6 months prior to enrollment; b) Previous and/or current presence of NYHA class III~IV congestive heart failure; c) Previous and/or current presence of severe cardiac arrhythmias requiring medication; 16. Presence of concomitant diseases or conditions that would result in a risk of adverse events during the study period: (8 small strips) a) Hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg) that is not well controlled even with standard treatment, and is clinically significant as judged by the investigator; b) previous hypertensive crisis or hypertensive encephalopathy; c) previous history of intracranial or spinal cord hemorrhage; d) Evidence of current bleeding tendency or severe coagulopathy (without anticoagulant therapy) or tumor involving large vessels; e) hemoptysis (≥ 1/2 teaspoon of bright red blood during each episode) or radiation enteritis bleeding or radiation bladder bleeding (such as bloody stool, hematuria or endoscopic bleeding tendency, etc.) within 3 months prior to enrollment; f) present evidence of free gas in the abdomen; g) Current presence of severe, non-healing or dehisced wounds, or untreated fractures; h) Any other illness that, as judged by the investigator, would result in an unacceptable risk of adverse events during study treatment. 17. Those who have previous and/or current interstitial lung disease, pneumoconiosis, drug-related pneumonia, severe impairment of lung function, etc., which may interfere with the detection and handling of suspected drug-related pulmonary toxicity. 18. HIV-positive patients; Active hepatitis B (HBsAg positive with HBV-DNA > 500 IU/ml or lower limit of detection at the site [only if the lower limit of detection at the site is higher than 500 IU/ml]), active hepatitis C (patients with positive HCV antibody but lower limit of detection at the site < site are allowed to be included). 19. Known active tuberculosis and known active syphilis infection. 20. Other active malignancies within 5 years prior to signing informed consent or at the same time (cured localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer and carcinoma in situ of the breast can be enrolled). 21. History of allogeneic hematopoietic stem cell transplantation or organ transplantation (except corneal transplantation). 22. Received a live vaccine within 4 weeks prior to enrollment. 23. Those who have participated in other clinical studies and used other clinical trial drugs within 4 weeks before enrollment, or other clinical trial drugs that are still within 5 drug half-lives. 24. Known patients have a history of psychotropic drug abuse, alcohol abuse or drug abuse, and a clear history of neurological or psychiatric disorders, including epilepsy or dementia or hepatic encephalopathy. 25. The patient is known to have been allergic to macromolecular protein preparations in the past. There are contraindications and hypersensitivity to any of the components of tislelizumab, cisplatin, paclitaxel. 26. Pregnant or lactating patients. 27. Patients who, in the opinion of the investigator, may increase the study-related risk, may interfere with the interpretation of the study results, etc., according to the judgment of the investigator, are not suitable for enrollment.

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