Combination Therapy for First Line Treatment of Advanced Cervical Cancer

Study Overview
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Brief Summary
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This is a single center phase 1 trail to observe safety and efficacy of Paclitaxel plus Cisplatin\Carboplatin, PD-L1 antibody Toripalimab and Anlotinib as first-line regimen to treat the patient with metastatic 、persistent or recurrent disease after radical surgery、radical platinum-based concurrent chemoradiotherapy or both (Stage IA-IVA).

Detailed Description
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Advanced cervical cancer patients with metastatic, persistent or recurrent disease after radical surgery、radical platinum-based concurrent chemoradiotherapy or both will be treated by Paclitaxel plus Cisplatin\Carboplatin, PD-L1 antibody Toripalimab and Anlotinib.

Official Title
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Combination of Paclitaxel, Cisplatin\Carboplatin With Toripalimab and Anlotinib for First Line Treatment of Advanced Cervical Cancer

Conditions
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Advanced Cervical Cancer

Intervention / Treatment
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* Drug: Anlotinib, Toripalimab, Paclitaxel, Cisplatin/ Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female patients aged≥18 years. Histologically confirmed cervical squamous cell carcinoma or adenocarcinoma, without uncontrolled pleural effusion or ascites. Patients with advanced or metastatic disease who have disease progression after radical surgery、radical platinum-based concurrent chemoradiotherapy or both （Stage IA-IVA）, with measurable lesions. ECOG performance status 0 or 2, expected lifetime≥3 months. Adequate organ function: Absolute neutrophil count (ANC) ≥1.5x109/L, White blood count ≥3.5x109/L, Platelets ≥100x109/L, Hemoglobin (Hb) ≥100g/L, ALT/AST ≤2.5x ULN (for patient with liver metastasis ALT/AST ≤5x ULN), Serum bilirubin ≤1.5x ULN, Serum creatinine ≤1.5x ULN. HBV infected patients (inactive/asymptomatic carrier, chronic or active) with HBV DNA<500IU/ml (or 2500 copies/ml). Pregnancy test of female patients with fertile activity should be negative within 7 days before enrollment. Patients should keep contraception during treatment. Willingness and ability to comply with the protocol for the duration of the study including scheduled visits, examinations, investigations and treatment plans with informed consent form. Exclusion Criteria: Pregnancy or children bearing potential. brain or meningeal metastasis. With second primary malignant diseases. With uncontrolled auto-immune diseases, interstitial pneumonia, ulcerative colitis, or patients who should receive long-term glucocorticoid treatment (>10mg/d prednisone). With uncontrollable complications Inadequate organ function Conditions which impact on pill taking (dysphagia, chronic diarrhea, bowel obstruction). known hypersensitivity reaction to any of the study drugs or components. Other unsuitable conditions determined by investigators.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Anlotinib 12mg qd. po. d1-d14 q3w Toripalimab 240mg ivgtt. d1 q3w Paclitaxel 135mg/m2 ivgtt. d1 q3w Cisplatin 50mg/m2 ivgtt. d1 q3w Carboplatin AUC=5 ivgtt. d1 q3w | Drug: Anlotinib, Toripalimab, Paclitaxel, Cisplatin/ Carboplatin<br>* This is a single-arm study with all patients receiving these four drugs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: adverse events as assessed by CTCAE v5.0 |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | 36 months | 
| Overall survival |  | 36 months | 
| Objective response rate |  | 36 months | 
| Disease control rate |  | 36 months | 
| Duration of response |  | 36 months |