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NCT Number: NCT06430658

Neoadjuvant Comprehensive Treatment for Unresectable Esophageal Cancer

Patients diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) that is deemed unresectable face a bleak prognosis. Recent phase 1/2 studies have demonstrated the efficacy and safety of augmenting neoadjuvant concurrent chemoradiotherapy with immunotherapy in treating resectable ESCC. The present study is a prospective, 3-arm, randomized trial that seeks to evaluate the efficacy of diverse conversion therapy modalities in patients with unresectable ESCC. The study objectives include R0 resection rate, treatment-related adverse events, morbidity and mortality, 1-year progression-free survival (PFS), and 1-year overall survival (OS) rates.

Tislelizumab is a humanized IgG4 monoclonal antibody with high affinity/specificity for programmed cell death protein 1 (PD-1). Tislelizumab was specifically engineered to minimize binding to FcɤR on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy.

This trial will provide valuable insights into the effectiveness of the three conversion therapy modalities and help to inform clinical decision-making for patients with unresectable locally advanced ESCC.

Recruiting

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

Beijing, 100021, China

Location status: Recruiting

Location contact

Xin Wang, MD

CONTACT

[email protected]

+861013311583220

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically confirmed sorely ESCC without other histology subtypes.
  • Thoracic esophageal cancer.
  • No prior anti-cancer treatment, including but not limited to surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy.
  • Borderline unresectable locally advanced ESCC deemed by investigators as suspicious of but not confirmed T4b according to the American Joint Committee on Cancer (AJCC) 8th edition staging classification or extracapsular lymph node involvement (ELNI).
  • The Karnofsky Performance Scale (KPS) ≥70.
  • Normal primary organ functions, including but not limited to hemoglobin (Hb) ≥ 100g/L; white blood cell (WBC) ≥ 3.5×10*9/L; neutrophil count (NEUT) ≥ 1.5×10*9/L; platelets (PLT) ≥ 100×10*9/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5×UNL; total bilirubin (TBIL) ≤ 1.5×UNL; creatinine ≤ 1.5UNL; blood urea nitrogen (BUN) ≤ 1.0×UNL.

Exclusion criteria

  • Synchronous and metachronous primary malignancies in but not limited to the upper aerodigestive tract, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix.
  • Patients have undergone any type of anti-cancer treatment.
  • Baseline clinical stage M1 per AJCC 8th edition of staging classification, including supraclavicular lymph node metastases.
  • Investigators assessed major vessel involvement with high-risk hemorrhage.
  • A higher probability of esophageal perforation during conversion therapy.
  • Active infectious diseases, including but not limited to tuberculosis, hepatitis B virus, or hepatitis C virus.
  • Allergic to anti-cancer agents, including but not limited to anti-PD-1 or chemotherapy agents.
  • Given cardiopulmonary dysfunction, patients can not tolerate conversion therapy or surgery.
  • Pregnant or lactating women and women of childbearing potential who lacked effective contraception.
  • Non-compliance with the inclusion criteria judged by investigators.

Treatment and study plan

Tislelizumab (BGB-A317) with chemoradiotherapy

Combination Product

Different sequences and methods of treatment to convert surgery

Primary outcomes

  1. R0 resection rate

    Time frame: 4 months

    Minimal distance tumor/circumferential resection margin (CRM) > 1 mm.

Secondary outcomes

  1. 1-year OS rate

    Time frame: 1 year after all treatment

    Defined as the proportion of patients still alive within one year from treatment initiation.

  2. 1-year PFS

    Time frame: 1 year after all treatment

    Defined as the proportion of patients without disease progression or death within one year from treatment initiation.

  3. Positive rate of circulating tumor DNA (ctDNA) in minimal residual disease (MRD) before and after neoadjuvant treatment and its correlation with the pathological response and disease progression during surveilance

    Time frame: 6 month

    To investigate whether ctDNA variation can be used for MRD predicting incidence of pathological incidence and monitoring tumor progression after surgery

  4. Incidence of Treatment-Emergent Adverse Events

    Time frame: 4 month

    Adverse event during chemoRT or immunotherapy

  5. Pathological response rate

    Time frame: 4 month

  6. Postoperative complications

    Time frame: 4 month

Study contacts

Contact information is provided by the study sponsor or research team.

Xin Wang, Doctor

CONTACT

[email protected]

13311583220

Ziyu Zheng, B.M

CONTACT

[email protected]

13552252161

Sponsors and collaborators

Lead sponsor

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Other

Registry information

Official study title

NEoadjuvant Total RX for Borderline Unresectable Esophageal Squamous Cell Carcinoma: a Prospective Randomized, Three-Arm, Open-Label Phase II Trial (NEXUS-2)

Acronym: NEXUS-2

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
May 28, 2024
Registry last updated
Dec 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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