Pd-1 Antibody Combined Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer

Study of Pd-1 Antibody in Combination With Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer

Cervical cancer is one of the major health problems for chinese women. Besides surgery and radiotherapy, neoadjuvant chemotherapy has been proved to be an effective program by many studies. However, not all patients respond well to neoadjuvant chemotherapy. This is an open-label, single-arm, multi-center clinical trial to evaluate whether PD-1 in combination with neoadjuvant chemotherapy will achieve better objective response rate.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Uterine Cervical Cancer; Uterine Cervical Neoplasm
• Intervention / Treatment: Drug: Cisplatin+Albumin-bound paclitaxel (1 cycle) and PD-1 monoclonal antibody+Cisplatin+Albumin-bound paclitaxel (2 cycles)

Detailed Description

Subjects will receive therapy Q3W until evaluation of efficacy. The first cycle include cisplatin and albumin-bound paclitaxel. A combination of anti-PD-1 antibody (SHR-1210) with cisplatin and albumin-bound paclitaxel would be given in second and third cycles. Patients who have demonstrated complete or partial tumour responses （CR/PR）will receive surgery and receive postoperative adjuvant therapy in accordance with NCCN guideline. Patients who have demonstrated stable disease or progressive disease （SD/PD）will receive concurrent radiochemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Tongji Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Patients with locally advanced (2019 FIGO staged IB3, IIA2 and IIB/IIIC1r（tumor size> 4cm) ) cervical cancer and had not received any treatment before.
2. Histologically confirmed squamous carcinoma, adenocarcinoma or adenosquamous carcinoma of the cervix.
3. Pathological examination of the PD-L1 positive（Combined score Positive Score≥1）.
4. Females 18-65 years of age.
5. Eastern Cooperative Oncology Group score 0-1.
6. WBC≥3.5*10^9/L, NEU≥1.5*10^9/L, Platelet≥80×10^9 /L; AST and ALT ≤1.5 times normal upper limit; Total bilirubin ≤1.5 times the upper limit of normal value; serum creatinine and blood urea nitrogen ≤the upper limit of normal value.
7. Well-compliance and willing to keep in touch.
8. Willing to participate in this study, and sign the informed consent.

Exclusion Criteria:

1. Active or known or suspected autoimmune disease requires a system treatment as follows but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction, asthma requiring intervention with bronchodilators.
2. HIV infection, active HBV/HCV.
3. Condition requiring systemic treatment with small doses of corticosteroids within 1 months or large doses of corticosteroids within 3 months prior to randomization.
4. Any primary malignancy within 5 years.
5. Participate in other drug clinical trials at the same time.
6. Pregnant or lactating female patients.
7. Comorbidity including but not limited to: heart diseases (grade III-IV cardiac insufficiency (NYHA standard); central nervous system diseases or nonfunctional behavior; hematological system diseases; liver or kidney malformation or history of surgery.
8. Drug or alcohol abuse.
9. Unable or unwilling to sign informed consents.
10. Not eligible for the study judged by researchers.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group; Patients receive 1 cycle of cisplatin and albumin-bound paclitaxel combined neoadjuvant chemotherapy and subsequent 2 cycles of PD-1 antibody combined neoadjuvant chemotherapy.	Drug: Cisplatin+Albumin-bound paclitaxel (1 cycle) and PD-1 monoclonal antibody+Cisplatin+Albumin-bound paclitaxel (2 cycles); PD-1 monoclonal antibody （SHR-1210)：200mg，IV infusion，Q3W Cisplatin：75-80 mg/m2, IV infusion, Q3W Albumin-bound paclitaxel: 260 mg/m2，30min，IV infusion, Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of the participants in the ITT population who have a Complete Response or Partial Response. The ORR will be assessed by a blind independent central reviewer per RECIST 1.1	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological response rate	Pathological response rate is defined as the percentage of the participants in the ITT population who have complete pathologic remission or the infiltration depth of cervical lesions was < 3mm in histological examination.	3 months
Overall survival （OS）	OS is defined as the time from the date of randomization until death.	5 years
Event-free survival (EFS)	EFS defined as the time interval from the date of randomization to disease progression, local or distant recurrence (in patients undergoing surgery), or death due to any cause.	5 years

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology
• Collaborators: Chongqing University Cancer Hospital; Peking University People's Hospital; Qilu Hospital of Shandong University; Women's Hospital School Of Medicine Zhejiang University; Tianjin Medical University General Hospital; Obstetrics & Gynecology Hospital of Fudan University; Harbin Medical University; First Affiliated Hospital of Chongqing Medical University; Army Medical University
• Investigators: Study Chair: Ding Ma, M.D., PhD, Tongji Hospital, Tongji Medical College, HUST

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): July 1, 2028

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: August 16, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

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; Uterine Cervical Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Antibodies; Cisplatin; Albumin-Bound Paclitaxel; Antibodies, Monoclonal
• Other Study ID Numbers: 2020-S112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: 5 years after completion of the study
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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