Anti-PD-1 Immunotherapy Combined With SBRT for Patients With Oligometastatic ESCC

Overview

The goal of this phase II clinical trial is to explore the efficacy and safety of anti-PD1 combined with stereotactic body radiation therapy (SBRT) for patients with oligometastatic esophageal squamous cell carcinoma. Participants will receive anti-PD1 and SBRT to the metastatic lesions which are amenable to the delivery of SBRT after 4~6 cycles of systemic chemotherapy and anti-PD-1.

Full Title of Study: “Phase 2 Study of Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy for Patients With Oligometastatic Esophageal Squamous Cell Carcinoma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 1, 2024

Interventions

  • Drug: PD-1 combined with SBRT
    • Anti-PD1 monoclonal antibody combined with SBRT. The SBRT defined as the radiation prescription with single dose equal or over 4Gy and the fractions less or equal to 10 fractions. BED equal or over 50Gy is required.

Arms, Groups and Cohorts

  • Experimental: PD-1 combined with SBRT for metastatic lesions
    • Participants will receive anti-PD1 and SBRT to the metastatic lesions which are amenable to the delivery of SBRT after 4~6 cycles of systemic chemotherapy and anti-PD-1. SBRT for the metastatic lesions shall be conducted within two months after the completion of systemic therapy. The prescription of SBRT is determined by the investigator and the BED is required to over 50Gy.

Clinical Trial Outcome Measures

Primary Measures

  • 1-year progression-free survival
    • Time Frame: 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 12 months
    • 1-year progression-free survival

Secondary Measures

  • 1-year overall survival
    • Time Frame: 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 12 months
    • 1-year overall survival
  • ORR
    • Time Frame: 3 months after SBRT (plus or minus 14 days)]
    • Overall response rate
  • Treatment-related adverse events
    • Time Frame: From the start of treatment to 2 year after the completion of treatment
    • Toxicity of treatment was evaluated according to CTCAE 4.0

Participating in This Clinical Trial

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) with less than five metastatic lesions within three organs; 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. At least one metastatic lesions amenable to the delivery of SBRT; 6. Estimated life expectancy >4 months; 7. 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; 8. 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 have spinal bone metastases combined with spinal cord compression; 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 radiotherapy 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; 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).

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Sun Yat-sen University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Mian XI, MD – Sun Yat-sen University
  • Overall Official(s)
    • Mian Xi, MD, Principal Investigator, Sun Yat-sen University
  • Overall Contact(s)
    • Mian Xi, MD, 02087340540, ximian@sysucc.org.cn

References

Liu Q, Zhu Z, Chen Y, Deng J, Ai D, Liu Q, Wang S, Wu S, Chen J, Zhao K. Phase 2 Study of Stereotactic Body Radiation Therapy for Patients with Oligometastatic Esophageal Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys. 2020 Nov 1;108(3):707-715. doi: 10.1016/j.ijrobp.2020.05.003. Epub 2020 May 14.

Liu S, Luo L, Zhao L, Zhu Y, Liu H, Li Q, Cai L, Hu Y, Qiu B, Zhang L, Shen J, Yang Y, Liu M, Xi M. Induction chemotherapy followed by definitive chemoradiotherapy versus chemoradiotherapy alone in esophageal squamous cell carcinoma: a randomized phase II trial. Nat Commun. 2021 Jun 29;12(1):4014. doi: 10.1038/s41467-021-24288-1.

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