Combining benmelstobart with radiochemotherapy for esophageal cancer treatment

A Randomized Controlled, Multicenter Clinical Study of Benmelstobart Combined With Radiochemotherapy Versus Radiochemotherapy as Neoadjuvant Treatment for Esophageal Squamous Cell Carcinoma

This study is testing if adding a new drug called benmelstobart to standard radiation and chemotherapy can help people with esophageal cancer have better treatment outcomes before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 5 sites (Shantou, Guangdong and 4 other locations)
• Trial ID: NCT06637163 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness and safety of benmelstobart when combined with radiochemotherapy as a neoadjuvant treatment for esophageal squamous cell carcinoma. Participants will be randomly assigned to receive either the combination treatment or standard radiochemotherapy alone. The study aims to evaluate the rate of pathological complete response (pCR) following treatment, with surgery scheduled 6-8 weeks after the neoadjuvant therapy. Additionally, it will compare low-dose versus standard-dose radiotherapy in conjunction with benmelstobart. This research may expand treatment options for patients with this type of cancer.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with resectable esophageal squamous cell carcinoma who have not received prior antitumor treatments.

Not a fit: Patients with advanced esophageal cancer or those who have previously undergone antitumor therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective neoadjuvant treatment option for patients with esophageal squamous cell carcinoma.

How similar studies have performed: Other studies have shown promise in combining targeted therapies with radiochemotherapy, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Patients voluntarily participate in this study and sign informed consent forms, with good compliance.
* Aged 18 years and older, regardless of gender.
* ECOG performance status: 0-1.
* Patients with histologically confirmed clinical stages T1-3N+M0 or T3NanyM0 of resectable esophageal squamous cell carcinoma.
* No prior antitumor treatment for esophageal cancer, including chemotherapy, hormone therapy, radiotherapy, or immunotherapy.
* Laboratory tests must meet the following criteria (within 7 days prior to baseline enrollment):

  1. Complete blood count: a. Hemoglobin (Hb) ≥ 90 g/L (no blood transfusion in the last 14 days); b. Neutrophil count (NEUT) ≥ 1.5 × 10\^9/L; c. Platelet count (PLT) ≥ 100 × 10\^9/L; d. White blood cell count (WBC) ≥ 3 × 10\^9/L;
  2. Biochemical tests: a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; b. Total bilirubin (TBIL) ≤ 1.5 × ULN; c. Serum creatinine (Cr) ≤ 1.5 × ULN (or creatinine clearance (CCr) ≥ 60 mL/min);
  3. Coagulation function: activated partial thromboplastin time (APTT), International normalized ratio (INR), prothrombin time (PT) ≤ 1.5 × ULN;
  4. Thyroid function: Thyroid-stimulating hormone (TSH) ≤ ULN (if abnormal, FT3 and FT4 levels should also be assessed; if FT3 and FT4 levels are normal, the patient can be enrolled);
  5. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ 50%;
* Female participants must agree to use contraception (e.g., intrauterine device \[IUD\], contraceptive pills, or condoms) during the study and for 6 months after the study ends; a negative serum pregnancy test must be obtained within 7 days prior to enrollment, and participants must not be breastfeeding. Male participants must also agree to use contraception during the study and for 6 months after the study ends.

Exclusion Criteria:

Participants with any of the following criteria will be excluded from the study:

* Presence of other malignant tumors (except for previously cured basal cell carcinoma of the skin).
* Diagnosis of cervical esophageal cancer.
* Severe hypersensitivity reactions following the administration of other monoclonal antibodies.
* Any active autoimmune disease or history of autoimmune disease (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis; asthma requiring bronchodilator intervention). However, patients with the following conditions may be included: vitiligo, psoriasis, alopecia that do not require systemic treatment, well-controlled type 1 diabetes, and hypothyroidism with normal thyroid function under replacement therapy.
* Use of immunosuppressants, systemic, or absorbable local hormone therapy to achieve immunosuppressive effects (doses \> 10 mg/day of prednisone or equivalent), and continuing use within 2 weeks of the first dose.
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
* Uncontrollable neurological symptoms from brain metastases, spinal cord compression, or carcinomatous meningitis occurring within 4 weeks prior to the first dose, or evidence of brain or leptomeningeal disease found on CT or MRI screening.
* Presence of any severe and/or uncontrolled disease, including:

  1. Acute or persistent myocardial ischemia or myocardial infarction, poorly controlled clinically significant arrhythmias, and NYHA class II or higher heart failure; LVEF \< 50%.
  2. Active or uncontrolled severe infections (≥ CTCAE grade 2 infections).
* Vaccination with preventive or attenuated vaccines within 4 weeks prior to the first dose.
* Any factors, as judged by the investigator, that could lead to premature termination of the study, such as other serious illnesses (including mental illness) requiring concurrent treatment, significant laboratory abnormalities, or family or social factors that could affect participant safety.
* For participants who are HBsAg (+) and/or HBcAb (+), HBV DNA must be \< 500 IU/mL (if the local center's lower limit of detection is higher than 500 IU/mL, the investigator may decide on enrollment based on specific circumstances) and must continue to receive effective anti-HBV treatment during the study, or must have initiated treatment with entecavir or tenofovir prior to the study drug.
* For participants who are HCV antibody positive, HCV-RNA testing is required; those with HCV-RNA \> 10\^3 copies/mL will be excluded.
* Positive HIV test.

Where this trial is running

Shantou, Guangdong and 4 other locations

• Cancer Hospital of Shantou University Medical College — Shantou, Guangdong, China (Recruiting)
• Liaoning Cancer Hospital and Institute — Shenyang, Liaoning, China (Recruiting)
• Zhongshan Hospital Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)
• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin Municipality, China (Recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Lijie Tan, Professor — Fudan University
• Study coordinator: Lijie Tan, Professor

Conditions Esophageal Squamous Cell Carcinoma