Neoadjuvant Comprehensive Treatment for Unresectable Esophageal Cancer

NCT06430658 | Recruiting Phase 2

• 1 other identifier: NEXUS-2
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Esophagus Cancer

Keywords

Esophagus Cancer; Chemoradiotherapy; conversion surgery; immunotherapy

Outcome Measures

Primary Outcomes (1)

• R0 resection rate

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

  4 months

Secondary Outcomes (6)

• 1-year OS rate

  1 year after all treatment

• 1-year PFS

  1 year after all treatment

• 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

  6 month

• Incidence of Treatment-Emergent Adverse Events

  4 month

• Pathological response rate

  4 month

Study Arms (3)

ChemoRT+Immuno

EXPERIMENTAL

Surgery was evaluated after chemoradiotherapy (40-41.4Gy/1.8-2Gy/20-23 fractions) followed by two cycles of chemotherapy and immunotherapy.For inoperable patients, immunotherapy was used as maintenance therapy

Combination Product: Tislelizumab (BGB-A317) with chemoradiotherapy

Immuno+ChemoRT

EXPERIMENTAL

Surgery was evaluated after two cycles of chemotherapy and immunotherapy followed by chemoradiotherapy(40-41.4Gy/1.8-2Gy/20-23 fractions).For inoperable patients, immunotherapy was used as maintenance therapy

Combination Product: Tislelizumab (BGB-A317) with chemoradiotherapy

ChemoRT

ACTIVE COMPARATOR

Surgery was evaluated after concurrent definitive chemoradiotherapy (50-50.4Gy/1.8-2Gy/25-28fractions) .For inoperable patients, immunotherapy was used as maintenance therapy

Combination Product: Tislelizumab (BGB-A317) with chemoradiotherapy

Interventions

Tislelizumab (BGB-A317) with chemoradiotherapy COMBINATION_PRODUCT

Different sequences and methods of treatment to convert surgery

ChemoRT; ChemoRT+Immuno; Immuno+ChemoRT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

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

Beijing, 100021, China

RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Central Study Contacts

Xin Wang, Doctor

CONTACT

13311583220; beryl_wx2000@163.com

Ziyu Zheng, B.M

CONTACT

13552252161; zy_zhengw@163.com

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: Principal Investigator

Study Record Dates

• First Submitted: May 13, 2024
• First Posted: May 28, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)