the Predictive Value of Immune Cell in Locally Advanced Cervical Cancer

An Exploratory Analysis of the Predictive Value of Immune Cell Using Single-cell Sequencing on the Outcome of Locally Advanced Cervical Cancer Treated by Concurrent Chemoradiotherapy Followed by PD-1 Inhibitor

To explore the predictive value of immune cells by single-cell sequencing on the outcome of locally advanced cervical cancer treated by concurrent chemoradiotherapy Followed by PD-1 inhibitor

Study Overview

• Status: Recruiting
• Conditions: Immunotherapy; Locally Advanced Cervical Carcinoma; Concurrent Chemoradiotherapy
• Intervention / Treatment: Radiation: Nab-paclitaxel/Platinum, Sintilimab

Detailed Description

Concurrent chemoradiotherapy is the standard treatment for patients with locally advanced cervical cancer, but the treatment failure rate is up to 40% in previous studies. Immunotherapy using PD-1 inhibitor showed an objective response rate of 12-50% in studies, and pembrolizumab was approved by the US Food and Drug Administration for patients with advanced PD-L1-positive cervical cancer who experienced progression during or after chemotherapy. And according to KEYNOTE-A18, the addition of PD-1 inhibitor Pembrolizumab to the current concurrent chemoradiotherapy improved the PFS of such group of patients. But the detailed change of immune cells (tumor microenvironment and PBMC) during treatment is unknown, and studies on the relationship between immune cells and treatment-related side effect and efficiency is also in need.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Yongrui Bai, Dr.; Phone Number: 86-2-68383459; Email: baiyongrui@renji.com

Study Locations

• China
  • Shanghai, China, 200127
    • Recruiting
    • Renji Hospital
    • Contact: Haiyan Chen, Dr; Phone Number: +862168383624; Email: chenhaiyan@renji.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

locally advanced cervical carcinoma

Description

Inclusion criteria:

1. Age between 18 and 75;
2. Untreated patients with pathologically proven locally advanced cervical cancer;
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

4. Adequate hematological, renal and hepatic functions:

   4.1 Hemoglobin > 8.0 g/dl 4.2 Neutrophils > 2000 cells/μl; Leukocytes > 4 × 109/L 4.3 Platelets > 100 × 109/Lg. 4.4 Serum urea nitrogen (BUN) ≤ 1.5 × upper normal limit (UNL) 4.5 Serum creatinine (Cr) ≤ 1.5 × upper normal limit (UNL) 4.6 Serum ALT/AST ≤ 2.5× UNL 4.7 Serum Total bilirubin ≤ 1.5× UNL

5. Life expectancy > 6 months
6. Eligible for concurrent chemoradiotherapy assessed by principle investigator;
7. No obvious active bleeding;
8. Written informed consent must be available before study registration

Exclusion criteria:

1. Recurrent or distant metastatic disease;
2. Prior malignancies (other than curable non-melanoma skin cancer) within 5 years;
3. Active autoimmune diseases requiring systemic treatment or other diseases requiring long-term use of substantial amount of hormones or other immunosuppressants;
4. Patients who need to receive systemic corticosteroids (dose equivalent to or higher than prednisone 10mg qd) or other immunosuppressants within 14 days before enrollment or during the study;
5. Vaccination of live attenuated vaccine 30 days before enrollment, or planned vaccination of live attenuated vaccine during the study;
6. Previous organ transplantation or HIV patients;
7. Allergic to macromolecular proteins /monoclonal antibodies, or to any test drug component;
8. Active acute or chronic viral hepatitis B or C. Hepatitis B virus (HBV) DNA> 2000IU/ml or 104 copies/ml; hepatitis C virus (HCV) RNA> 103 copies/ml.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change of immune cells in the blood after chemoradiotherapy and immunotherapy	through single-cell sequence and data analysis, the investigators will focus on the percentage of each sub-type of immune cells after treatment, differential gene expression profiles in special cell type after chemoradiotherapy and immunotherapy.	1 year
the predictive value of the changed immune cell subtype in the blood on the side effect of immunotherapy	the investigators will focus on the occurrence and grade of side effect from immunotherapy according to the NCCN clinical practice guidelines in the evaluation and management of immunotherapy-related toxicity (through the symptoms, physical examination, and also through blood/image/endoscopy examination, such as blood routine, liver and renal function, TSH/T3/T4/ACTH concentration, myocardial enzymes concentration, EKG, echocardiography, CT/MRI, et al). And through statistical analysis, the investigators try to figure out if there is any immune subtype or any special molecular to a possible biomarker of the occurrence of any immunotherapy-related side effect.	1 year
the predictive value of the changed immune cell subtype in the blood on the effect of chemoradiotherapy and immunotherapy	through statistical analysis, the investigators try to figure out if there is any immune subtype or any special molecular to a possible biomarker of disease control (disease progression or not accordingly to the RECIST criterion)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change of immune cells in the tissue after chemoradiotherapy	through single-cell sequence and data analysis, the investigators will focus on the percentage of each sub-type of immune cells in the tumor microenvironment and differential gene expression profiles in special cell type after chemoradiotherapy.	1 year
the predictive value of the changed immune cell subtype in the tissue on the effect of chemoradiotherapy and immunotherapy	through statistical analysis, the investigators try to figure out if there is any immune subtype or any special molecular in the tumor tissue to a possible biomarker of disease control (disease progression or not accordingly to the RECIST criterion)	2 years
the predictive value of the changed immune cell subtype in the tumor microenvironment on the side effect of immunotherapy	through statistical analysis, the investigators try to figure out if there is any immune subtype or any special molecular in the tumor tissue to a possible biomarker of the occurrence of any immunotherapy-related side effect.	1 year

Collaborators and Investigators

• Sponsor: RenJi Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 18, 2024
• First Posted (Actual): April 23, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: KY2021-268-B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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