Tislelizumab Plus TP as Neoadjuvant Therapy for Local Advanced Cervical Carcinoma

Phase 1

• Conditions: Cervical Squamous Cell Carcinoma
• Interventions: Drug: Tislelizumab, paclitaxel/docetaxel, cisplatin/carboplatin

• Registration Number: NCT05013268
• Lead Sponsor: Ruijin Hospital

Brief Summary

The goal of this clinical trail is to investigate the efficacy and safety of PD-1 antibody Tislelizumab plus TP regimen (taxane combined with platinum) as neoadjuvant therapy for patients diagnosed as local advanced cervical carcinoma (FIGO staging IB2-IIB).

Detailed Description

This phase I study is being conducted to establish efficacy and safety of Tislelizumab plus TP regimen (taxane combined with platinum) as neoadjuvant therapy for patients diagnosed as local advanced cervical carcinoma (FIGO staging IB2-IIB).

All enrolled patients will receive same intervention. Treatment naïve patients who are diagnosed as local advanced cervical squamous cell carcinoma will receive Tislelizumab plus TP regimen before surgery for 3 cycles. After treatment, radiographic evaluation will be performed to assess clinical efficacy. Patients who have objective response will undergo radical surgery. Patients who are disease stable or progression will undergo radical chemoradiotherapy. The primary endpoint is major pathological response rate (MPR).

Study Timeline

• Status Verified: 2021-08
• Study First Submitted: 2021-08-17
• Study First Submitted QC: 2021-08-18
• Last Update Submitted: 2021-08-18
• Study First Posted: 2021-08-19
• Last Update Posted: 2021-08-24
• Study Start: 2021-09
• Primary Completion: 2022-06
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 15

Inclusion Criteria

1. Histologically confirmed cervical squamous cell carcinoma.
2. Clinical staging FIGO IB2-IIB, treatment naive.
3. Female patients aged≥18 years.
4. ECOG performance status 0 or 1, expected lifetime≥3 months.
5. Adequate organ function: Absolute neutrophil count (ANC) ≥1.5x109/L, White blood count ≥3.5x109/L, Platelets ≥75x109/L, Hemoglobin (Hb) ≥90g/L, ALT/AST ≤2.5x ULN, Serum bilirubin ≤1.5x ULN, Serum creatinine ≤1.5x ULN.
6. HBV infected patients (inactive/asymptomatic carrier, chronic or active) with HBV DNA<500IU/ml (or 2500 copies/ml).
7. Pregnancy test of female patients with fertile activity should be negative within 7 days before enrollment. Patients should keep contraception during treatment.
8. 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

1. Pregnancy or children bearing potential.

2. brain or meningeal metastasis.

3. With second primary malignant diseases.

4. With uncontrolled auto-immune diseases, interstitial pneumonia, ulcerative colitis, or patients who should receive long-term glucocorticoid treatment (>10mg/d prednisone).

5. With uncontrollable complications

6. Inadequate organ function

7. Known hypersensitivity reaction to any of the study drugs or components.

8. Other unsuitable conditions determined by investigators.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Tislelizumab plus TP regimen as neoadjuvant therapy for local advanced cervical carcinoma	Tislelizumab, paclitaxel/docetaxel, cisplatin/carboplatin	Experimental: Tislelizumab, paclitaxel/docetaxel, cisplatin/carboplatin The subjects enrolled in this trial will receive tislelizumab 200mg ivgtt d1, paclitaxel (175mg/m2 ivgtt d1) or docetaxel (75mg/m2 ivgtt d1), cisplatin (75mg/m2 ivgtt d1) or carboplatin (AUC=5 ivgtt d1). The regimen will be repeated every 3 weeks for 3 cycles. Chemotherapy regimen will be selected by investigators. Subjects will be enrolled serially.

Primary Outcome Measures

Name	Time	Method
Major pathological response (MPR) rate	Up to approximately 8 weeks following completion of neoadjuvant treatment	Major pathological response rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes following completion of neoadjuvant therapy.

Secondary Outcome Measures

Name	Time	Method
Relapse free survival (RFS)	Up to approximately 36 months	Relapse free survival is defined as the time from surgery to first local, regional, or distant tumor recurrence or metastasis, or deaths.
Overall survival (OS)	Up to approximately 60 months	Overall survival is defined as the time from signing ICF until death from any cause.
Pathological Complete Response (pCR) Rate	Up to approximately 8 weeks following completion of neoadjuvant treatment	rate is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy.
Objective response rate (ORR)	Up to 30 days after last completion of neoadjuvant treatment	Objective Response Rate is defined as the percentage of patients with a documented complete response or partial response (CR + PR) based on RECIST v1.1.
Adverse Events	Up to approximately 12 months	All patients who have received at least one dose of treatment will be included in the safety analysis. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Disease free survival (DFS)	Up to approximately 36 months	disease-free survival (DFS) is defined as surgery until documented disease recurrence or death from any cause in all patients (ITT population) who undergo surgery

Trial Locations

Locations (1)

Ruijin Hospital, Shanghai JiaoTong University School of Medicine; 🇨🇳 Shanghai, China