NCT05520619

Brief Summary

Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer (EC). However, as high as more than 40% of EC patients experienced locoregional recurrence after concurrent CRT. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. Recently, the combination of immunotherapy with CRT has emerged as a promising strategy to improve clinical outcomes in EC. The aim of this study was to evaluate whether the efficacy of tislelizumab (an anti-PD-1 antibody) plus induction chemotherapy followed by concurrent chemoradiotherapy would achieve a ≥71% 1-year progression-free survival rate, surpassing the historical 56% rate (NCT02403531) in patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
114

participants targeted

Target at P50-P75 for phase_2

Timeline
3mo left

Started Sep 2022

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress94%
Sep 2022Jul 2026

First Submitted

Initial submission to the registry

August 21, 2022

Completed
9 days until next milestone

First Posted

Study publicly available on registry

August 30, 2022

Completed
16 days until next milestone

Study Start

First participant enrolled

September 15, 2022

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 10, 2025

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2026

Expected
Last Updated

November 18, 2024

Status Verified

November 1, 2024

Enrollment Period

3.2 years

First QC Date

August 21, 2022

Last Update Submit

November 14, 2024

Conditions

Esophageal Squamous Cell CarcinomaLocally Advanced Esophageal Squamous Cell Carcinoma

Keywords

Esophageal Squamous Cell CarcinomaInduction chemotherapyDefinitive chemoradiotherapyTislelizumab

Outcome Measures

Primary Outcomes (1)

  • Progression-free survival

    Two-year follow-up from the date of randomization to the date of disease progression or last follow-up

    From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.

Secondary Outcomes (4)

  • Overall survival

    From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 24 months.

  • Duration of response

    From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 24 months

  • Clinical complete response

    Three months after the treatment (plus or minus 7 days)

  • Treatment-related adverse events

    From date of randomization until the date of last follow-up, assessed up to 12 months.

Other Outcomes (4)

  • PD-L1 expression

    From date of randomization until the date of last follow-up, assessed up to 24 months.

  • ctDNA at baseline, during, and after treatment

    From date of randomization until the date of last follow-up, assessed up to 24 months.

  • CD8 expression at baseline

    From date of randomization until the date of last follow-up, assessed up to 24 months.

  • +1 more other outcomes

Study Arms (2)

Tislelizumab plus CRT with maintenance

EXPERIMENTAL

Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135-175 mg/m2, cisplatin 75 mg/m2, and tislelizumab 200mg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with paclitaxel 45mg/m2 and cisplatin 25 mg/m2 once weekly for 5 weeks and 2 cycles of tislelizumab. Patients in Arm A will receive 12 additional cycles of tislelizumab after the completion of radiotherapy.

Drug: Paclitaxel, CisplatinDrug: tislelizumabRadiation: Radiotherapy

Tislelizumab plus CRT without maintenance

EXPERIMENTAL

Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135-175 mg/m2, cisplatin 75 mg/m2, and tislelizumab 200mg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with paclitaxel 45mg/m2 and cisplatin 25 mg/m2 once weekly for 5 weeks and 2 cycles of tislelizumab. Patients in Arm B will receive 4 cycles of tislelizumab in total.

Drug: Paclitaxel, CisplatinDrug: tislelizumabRadiation: Radiotherapy

Interventions

Paclitaxel, CisplatinDRUG

Patients received 2 cycles of induction chemotherapy with paclitaxel/cisplatin (paclitaxel 135-175mg/m2 and cisplatin 75 mg/m2) prior to radiotherapy. Then patients will receive paclitaxel 45mg/m2 and cisplatin 25 mg/m2 once weekly for 5 weeks during radiotherapy.

Also known as: Taxol
Tislelizumab plus CRT with maintenanceTislelizumab plus CRT without maintenance
tislelizumabDRUG

Patients received tislelizumab 200 mg every 3 weeks for 16 cycles in Arm A and 4 cycles in Arm B.

Tislelizumab plus CRT with maintenanceTislelizumab plus CRT without maintenance
RadiotherapyRADIATION

All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks.

Also known as: intensity-modulated radiotherapy
Tislelizumab plus CRT with maintenanceTislelizumab plus CRT without maintenance

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed squamous cell carcinoma of the esophagus;
  • Locally advanced, and absence of hematogenous metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan (according to UICC TNM version 8);
  • Not suitable for surgery (either for medical reasons or patient's choice);
  • Age at diagnosis 18 to 70 years;
  • No prior cancer therapy;
  • Estimated life expectancy \>6 months;
  • Eastern Cooperative Oncology Group performance status ≤ 2
  • No history of concomitant or previous malignancy;
  • The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥4.0×109/L, absolute neutrophil count (ANC) ≥1.5×109/L; b. platelets ≥100×109/L; c. hemoglobin ≥9g/dL; d. serum albumin ≥2.8g/dL; e. total bilirubin ≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. serum creatinine ≤1.5×ULN or creatinine clearance rate \>60 mL/min;
  • Ability to understand the study and sign informed consent.

You may not qualify if:

  • Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
  • Patients with hematogenous metastasis disease at diagnosis;
  • Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
  • Patients who have a preexisting or coexisting bleeding disorder;
  • Female patients who are pregnant or lactating;
  • Inability to provide informed consent due to psychological, familial, social and other factors;
  • Presence of CTC grade ≥ 3 peripheral neuropathy;
  • A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
  • A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
  • Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
  • Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;
  • A history of interstitial lung disease or non-infectious pneumonia;
  • A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;
  • Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Mian Xi

Guangzhou, Guangdong, 510060, China

Location

Related Publications (2)

  • Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4.

    PMID: 34454674BACKGROUND

  • Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):916-925. doi: 10.1001/jama.2021.12836.

    PMID: 34519801BACKGROUND

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

TP protocolPaclitaxeltislelizumabRadiotherapyRadiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms, Squamous CellEsophageal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesTherapeuticsRadiotherapy, ConformalRadiotherapy, Computer-Assisted

Study Officials

  • Ruihua Xu, MD

    Sun Yat-sen University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

August 21, 2022

First Posted

August 30, 2022

Study Start

September 15, 2022

Primary Completion

November 10, 2025

Study Completion (Estimated)

July 31, 2026

Last Updated

November 18, 2024

Record last verified: 2024-11

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)