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

Primary Purpose

Esophageal Squamous Cell Carcinoma, Oligometastatic Disease

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
PD-1 combined with SBRT
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring esophageal cancer; oligometastases; PD-1; SBRT

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Eastern Cooperative Oncology Group performance status ≤ 2; Histologically confirmed squamous cell carcinoma of the esophagus; Diagnosed with stage IVB disease (according to UICC TNM version 8) with less than five metastatic lesions within three organs; 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; At least one metastatic lesions amenable to the delivery of SBRT; Estimated life expectancy >4 months; 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; Ability to understand the study and sign informed consent. Exclusion Criteria: Progression was confirmed after completion of 4 to 6 cycles of standard chemotherapy and anti-PD1 treatment; Patients with intracranial metastasis disease at diagnosis; History of thoracic irradiation; Known or suspected allergy or hypersensitivity to monoclonal antibodies and the chemotherapeutic drugs: Capecitabine, paclitaxel, or platinum; Patients have spinal bone metastases combined with spinal cord compression; A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer; Patients who cannot tolerate radiotherapy due to severe cardiac, lung, liver, or kidney dysfunction, or hematopoietic disease or cachexia; Inability to provide informed consent due to psychological, familial, social, and other factors; Female patients who are pregnant or during lactation; 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; 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).

Sites / Locations

  • Mian XiRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PD-1 combined with SBRT for metastatic lesions

Arm Description

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.

Outcomes

Primary Outcome Measures

1-year progression-free survival
1-year progression-free survival

Secondary Outcome Measures

1-year overall survival
1-year overall survival
ORR
Overall response rate
Treatment-related adverse events
Toxicity of treatment was evaluated according to CTCAE 4.0

Full Information

First Posted
November 17, 2022
Last Updated
December 18, 2022
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT05626569
Brief Title
Anti-PD-1 Immunotherapy Combined With SBRT for Patients With Oligometastatic ESCC
Official Title
Phase 2 Study of Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy for Patients With Oligometastatic Esophageal Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 10, 2022 (Actual)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
July 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma, Oligometastatic Disease
Keywords
esophageal cancer; oligometastases; PD-1; SBRT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PD-1 combined with SBRT for metastatic lesions
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PD-1 combined with SBRT
Other Intervention Name(s)
SBRT
Intervention Description
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.
Primary Outcome Measure Information:
Title
1-year progression-free survival
Description
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
Secondary Outcome Measure Information:
Title
1-year overall survival
Description
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
Title
ORR
Description
Overall response rate
Time Frame
3 months after SBRT (plus or minus 14 days)]
Title
Treatment-related adverse events
Description
Toxicity of treatment was evaluated according to CTCAE 4.0
Time Frame
From the start of treatment to 2 year after the completion of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Eastern Cooperative Oncology Group performance status ≤ 2; Histologically confirmed squamous cell carcinoma of the esophagus; Diagnosed with stage IVB disease (according to UICC TNM version 8) with less than five metastatic lesions within three organs; 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; At least one metastatic lesions amenable to the delivery of SBRT; Estimated life expectancy >4 months; 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; Ability to understand the study and sign informed consent. Exclusion Criteria: Progression was confirmed after completion of 4 to 6 cycles of standard chemotherapy and anti-PD1 treatment; Patients with intracranial metastasis disease at diagnosis; History of thoracic irradiation; Known or suspected allergy or hypersensitivity to monoclonal antibodies and the chemotherapeutic drugs: Capecitabine, paclitaxel, or platinum; Patients have spinal bone metastases combined with spinal cord compression; A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer; Patients who cannot tolerate radiotherapy due to severe cardiac, lung, liver, or kidney dysfunction, or hematopoietic disease or cachexia; Inability to provide informed consent due to psychological, familial, social, and other factors; Female patients who are pregnant or during lactation; 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; 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mian Xi, MD
Phone
02087340540
Email
ximian@sysucc.org.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Baoqing Chen, MD
Phone
02087340540
Email
chenbq@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mian Xi, MD
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mian Xi
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Baoqing Chen
Phone
02087340540
Email
chenbq@sysucc.org.cn

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32417405
Citation
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.
Results Reference
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PubMed Identifier
34188053
Citation
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.
Results Reference
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Anti-PD-1 Immunotherapy Combined With SBRT for Patients With Oligometastatic ESCC

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