Efficacy of Neoadjuvant PD-1 Blockade Plus Chemotherapy for Esophageal Squamous Cell Carcinoma

January 31, 2021 updated by: Jun Liu, Guangzhou Institute of Respiratory Disease

The Efficacy of Neoadjuvant PD-1 Plus Concurrent Chemotherapy for Stage II-IVA Operable Esophageal Squamous Cell Carcinoma：A Single Armed, Open-label, Multicentre, Clinical Trial

This study aims to evaluate the efficacy of Camrelizumab plus concurrent chemotherapy as neoadjuvant approach for patients with opearble esophageal squamous cell carcinoma. In addition, potential clinical utility of ctDNA in monitoring tumor burden and dynamics of tumor clonality during neoadjuvant immunotherapy will be assessed as well. At the same time, CD8 and PD-L1 will also be used as monitoring indicators.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Immunotherapy improves clinical outcome of patients with advanced stage or metastatic esophageal squamous cell carcinoma (ESCC). In addition, superior effect of immunotherapy for esophageal squamous cell carcinoma was also reported recently. While, clinical application of ctDNA, PD-L1 and CD8 T cell monitoring in neoadjuvant immunotherapy for patients with esophageal squamous cell carcinoma is largely unknown. This trial will evaluate firstly the efficacy and the safety of Camrelizumab plus chemotherapy （albumin-bound paclitaxel plus cisplatin）as neoadjuvant approach. The evaluation indicators include pathological complete response rate (pCR) and objective imaging response rate after neoadjuvant therapy (ORR). ), 2-year progression-free survival (2y-PFS), postoperative progression-free survival (PFS), and overall survival (OS) after treatment. Objective response rate (ORR) based upon immune-Response Evaluation Criteria in Solid Tumors Version (RECIST v1.1). Major pathological response assessed by post-operational pathological review ctDNA efficacy will also be evaluated along with clinical management. Monitoring tumor burden, clonality as well as tumor heterogeneity evaluation will be correlated to radiological assessment and pathological findings.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China
        • Jingpei Li

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female patients aged ≥18 years, ≤70 years.
  • Gastroscope/ultrasound gastroscopy biopsy, Histologically or cytologically confirmed esophageal squamous cell carcinoma. Clinically diagnosed as II-IVA esophageal squamous cell carcinoma (cT2N1-3M0/cT3N0-3M0/cT4N0-3M0).
  • Non-Cervical Esophageal Cancer
  • Previously received no systemic or topical treatment for esophageal cancer, at least one measurable lesion for neoadjuvant treatment imaging evaluation according to RECIST 1.1;
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Estimated survival time ≥ 12 months;
  • Subjects had no major organ dysfunction, and the investigators assessed thyroid, lung, liver, kidney function, and cardiac function as normal.
  • Women of childbearing age must have taken reliable Contraception or have the negative predictive value of urine/ serum pregnancy test within 7 days prior to enrollment. They are also willing to use appropriate methods of contraception during the trial and 8 weeks after the last administration of the test drugs. For men, They must agree to use contraception or surgical sterilization during the trial and 8 weeks after the last administration of the test drug.
  • Subjects voluntarily joined the study and signed informed consent. patients who accept blood sample collection at multiple time points. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.

Exclusion Criteria:

  • Have a history of gastrectomy or have surgical contraindications
  • The investigator assessed that the patient had other serious illnesses that may affect follow-up and short-term survival;
  • There are any active autoimmune diseases or a medical history of autoimmune (including, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, thyroid function Decreased. Subjects with vitiligo or adults who have had childhood asthma but have fully relieved without any intervention may be included. However, subjects who require bronchodilators for medical intervention cannot be included.)
  • Cardiac clinical symptoms or diseases that are not well controlled, such as: a. Heart Failure NYHA > Class Ⅱ, b. unstable angina, c. myocardial infarction within 1 year; d. Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
  • Subjects with congenital or acquired immunodeficiency (such as HIV-infected), or active hepatitis (hepatitis B reference: HBsAg-positive, HBV DNA ≥ 2000 IU/ml or copy number ≥ 104/ml; hepatitis C reference: HCV antibody-positive.)
  • Uncontrollable history of diabetes;
  • Patients who have used other clinical trial study drugs within 4 weeks prior to the first dose.
  • Severe allergic reactions to monoclonal antibodies or allergy to paclitaxel or human albumin.
  • Peripheral blood neutrophil count is less than 1500/mm3
  • Patients who have received or are undergoing other chemotherapy, radiation therapy or targeted therapy.
  • According to the investigator's assessment, there are other factors that may lead to the termination of the study, such as other serious diseases (including mental illness) requiring combined treatment. Any other condition and social/psychological problems, etc., the investigator judged that the patient was not suitable for participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: camrelizumab plus concurrent chemotherapy
Neoadjuvant immunotherapy, PD-1, plus concurrent chemotherapy（albumin-bound paclitaxel + Cisplatin） will be applied to patients with operable esophageal squamous cell carcinoma before surgery.
Drug: camrelizumab
Participants will receive camrelizumab, 200mg, intravenously over 30 - 60 minutes, day 1 of every 3 weeks for 6 weeks. Discontinuation will be considered due to toxicity, withdrawal of consent, or end of study. Every 3-week treatment period was considered to be a cycle.
Other Names:
  • SHR-1210
Drug: Paclitaxel for injection (albumin-bound)
Paclitaxel for injection (albumin-bound): 260mg/m2(in total), ivgtt d1, d8, q3w，for 2 cycle
Other Names:
  • paclitaxel
Drug: Cisplatin
75mg/m2(in total), ivgtt d1-d3, q3w, for 2 cycles
Other Names:
  • CDDP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic complete remission (PCR)
Time Frame: 4 weeks after surgery
Primary tumor or lymph node surgery specimen pathological examination without residual tumor cell
4 weeks after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: At the end of Cycle 2 (each cycle is 21 days)
Objective Response Rate Determine the tumor shrinkage rate, tumor boundary and the adhesion of tumor
At the end of Cycle 2 (each cycle is 21 days)
2-year progression-free survival (PFS)
Time Frame: every 2 months (up to 24 months)
From date of surgery until the date of first documented progression or date of death from any cause
every 2 months (up to 24 months)
Progression-free survival (PFS)
Time Frame: every 2 months (up to 24 months)
From date of surgery until the date of first documented progression or date of death from any cause
every 2 months (up to 24 months)
Overall survival (OS)
Time Frame: every 2 months (up to 24 months)
Defined from date of Signing ICF to date of first documentation of death from any cause or censored at the date of the last follow-up.
every 2 months (up to 24 months)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
safety of neoadjuvant PD-1 Blockade Plus Chemotherapy
Time Frame: Every 3 weeks (up to 3 months after surgery)
Incidence of grade 3-5 adverse events [Safety and Tolerability]
Every 3 weeks (up to 3 months after surgery)
Evaluation of molecular features and ctDNA changing in pre, per and post-treatment plasma
Time Frame: every 2 months (up to 12 months)
All DNA samples were tested to calculate single nucleotide variants (SNV's), small insertions or deletions (Indels), copy number variations (CNV's), splice variations (SV's), gene fusions (GF's), tumor mutation burden (TMB) and micro-satellite instability (MSI) and others value by all enrolled. NGS (Next generation sequencing)-panel (688 genes) for monitoring on post-treatment residual disease in order to identify mechanisms of response. Measurement of different baseline ctDNA for their prognostic value.
every 2 months (up to 12 months)
Evaluation of Immunomicroenvironment changing in pre, per and post-treatment plasma
Time Frame: every 2 months (up to 12 months)
the tumor immune microenvironment evaluated with multiplexed immunohistochemistry (mIHC), The evaluation of immune microenvironment uses the method of multiple immunofluorescence, through the detection of CD8, CD163, CD68, PD-1 and PD-L1 four bio-markers, determine the situation of related immune cells in the process and efficacy.
every 2 months (up to 12 months)
perioperative adverse events
Time Frame: Time to discharge or 30 days of in hospital stay whichever came first
The participants were followed up daily and perioperative adverse events as defined by the American College of Surgeons National Quality Improvement Program. The participants were followed up until discharge or 30 days of in hospital stay and the secondary outcome measures entered into a questionnaire.
Time to discharge or 30 days of in hospital stay whichever came first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangzhou Institute of Respiratory Disease

Collaborators

Jiangsu HengRui Medicine Co., Ltd.
BGI-Shenzhen

Investigators

  • Study Chair: Jun liu, Ph.D, M.D, The First Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 17, 2020

Primary Completion (Actual)

January 15, 2021

Study Completion (Actual)

January 31, 2021

Study Registration Dates

First Submitted

December 23, 2019

First Submitted That Met QC Criteria

January 8, 2020

First Posted (Actual)

January 13, 2020

Study Record Updates

Last Update Posted (Actual)

February 2, 2021

Last Update Submitted That Met QC Criteria

January 31, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIC-ESCC2019

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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