Chemoradiotherapy combined with anti-PD-1 for advanced esophageal cancer

Systemic Therapy Combined With Thoracic Concurrent Chemoradiotherapy Versus Systemic Therapy Alone in Stage IVB Esophageal Squamous Cell Carcinoma: A Prospective Randomized Phase II Study

This study is testing if combining radiation therapy with a cancer drug and immunotherapy can help people with advanced esophageal cancer live longer and feel better compared to standard treatment alone.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 126 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05512520 on ClinicalTrials.gov

What this trial studies

This phase II study evaluates the effectiveness and safety of combining intensity-modulated radiotherapy with capecitabine and anti-PD-1 therapy for patients with stage IVB esophageal squamous cell carcinoma. The study aims to determine if this combination improves survival and quality of life compared to systemic therapy alone. Participants will be randomly assigned to receive either the combined treatment or standard systemic therapy, with a focus on those with non-regional lymph node metastasis. The study builds on previous retrospective findings suggesting improved outcomes with concurrent chemoradiotherapy.

Who should consider this trial

Good fit: Ideal candidates include patients with stage IVB esophageal squamous cell carcinoma who have not shown disease progression after initial chemotherapy and anti-PD-1 treatment.

Not a fit: Patients who have experienced disease progression after initial chemotherapy and anti-PD-1 treatment will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly enhance survival rates and quality of life for patients with advanced esophageal cancer.

How similar studies have performed: Previous studies have suggested positive outcomes with similar treatment combinations, but this study is among the first to prospectively evaluate this specific approach.

Eligibility criteria

Inclusion Criteria:

1. Eastern Cooperative Oncology Group performance status ≤ 2
2. Histologically confirmed squamous cell carcinoma of the esophagus;
3. Diagnosed with stage IVB disease (according to UICC TNM version 8);
4. Received 4 to 6 cycles of standard chemotherapy (fluoropyrimidine or taxane-based platinum doublet chemotherapy) and anti-PD1 treatment, and no progression disease was confirmed;
5. Estimated life expectancy \>4 months;
6. The function of important organs meet 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;
7. Ability to understand the study and sign informed consent.

Exclusion Criteria:

1. Progression was confirmed after completion of 4 to 6 cycles of standard chemotherapy and anti-PD1 treatment;
2. Patients with intracranial metastasis disease at diagnosis;
3. History of thoracic irradiation;
4. Known or suspected allergy or hypersensitivity to monoclonal antibodies and the chemotherapeutic drugs: Capecitabine, paclitaxel, or platinum;
5. Patients who have a preexisting esophagomediastinal fistula and/or esophagotracheal fistula;
6. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
7. Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver, or kidney dysfunction, or hematopoietic disease or cachexia.
8. Inability to provide informed consent due to psychological, familial, social, and other factors;
9. Female patients who are pregnant or during lactation;
10. 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;
11. A history of interstitial lung disease or non-infectious pneumonia;
12. 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).

Where this trial is running

Guangzhou, Guangdong

• Sun yat-sen University Cancer center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Mian Xi, MD

Conditions Metastatic Esophageal Squamous Cell Carcinoma; metastatic esophageal squamous cell carcinoma; anti-PD-1; Capecitabine; chemoradiotherapy