Tislelizumab Plus TP as Neoadjuvant Therapy for Local Advanced Cervical Carcinoma (TiTanec)

The Efficacy and Safety of Tislelizumab Combined With Taxanes and Platinum as Neoadjuvant Therapy for Patients With Local Advanced Cervical Carcinoma， an Open Lable，Single-center, Exploratory Clinical Trial

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Tislelizumab, paclitaxel/docetaxel, cisplatin/carboplatin

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 Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yan Shi; Phone Number: 13810561979; Email: sy_rjh@aliyun.com

Study Locations

• China
  • Shanghai, China
    • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
    • Contact: Chenfei Zhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

9. Other unsuitable conditions determined by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tislelizumab plus TP regimen as neoadjuvant therapy for local advanced cervical carcinoma; 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.

Drug: Tislelizumab, paclitaxel/docetaxel, cisplatin/carboplatin; Drug: Tislelizumab 200mg, d1, ivgtt, every 3 weeks, for 3 cycles; Drug: Paclitaxel; docetaxel Dose: 175mg/m2 d1; 75mg/m2 d1, every 3 weeks, for 3 cycles Other Name: none; Drug: Cisplatin; Carboplatin Dose: 75mg/m2 d1; AUC=5, d1, every 3 weeks, for 3 cycles Other Name: none

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response (MPR) rate	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.	Up to approximately 8 weeks following completion of neoadjuvant treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR) Rate	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.	Up to approximately 8 weeks following completion of neoadjuvant treatment
Objective response rate (ORR)	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.	Up to 30 days after last completion of neoadjuvant treatment
Relapse free survival (RFS)	Relapse free survival is defined as the time from surgery to first local, regional, or distant tumor recurrence or metastasis, or deaths.	Up to approximately 36 months
Disease free survival (DFS)	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	Up to approximately 36 months
Adverse Events	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	Up to approximately 12 months
Overall survival (OS)	Overall survival is defined as the time from signing ICF until death from any cause.	Up to approximately 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers analysis	The association between biomarkers expression (eg. PD-L1 CPS) in primary tumor and efficacy.	Up to approximately 12 months

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Yan Shi, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: August 17, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 19, 2021

Study Record Updates

• Last Update Posted (Actual): August 24, 2021
• Last Update Submitted That Met QC Criteria: August 18, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Docetaxel; Carboplatin; Paclitaxel; Cisplatin
• Other Study ID Numbers: TiTanec

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No