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SI-B001 Combined With Irinotecan in the Treatment of Recurrent Metastatic Esophageal Squamous Cell Carcinoma.

Primary Purpose

Esophageal Squamous Cell Carcinomas

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
SI-B001
Irinotecan
Sponsored by
Sichuan Baili Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinomas focused on measuring ESCC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female, age: ≥18 years and ≤75 years;
  2. Expected survival time ≥3 months;
  3. Locally advanced esophageal squamous cell carcinoma confirmed histologically or pathologically as recurrent or metastatic or without indications of radical local treatment;
  4. Patients who had failed or were intolerant to prior anti-PD-1 (L1) mab or anti-PD-1 (L1) mab combined with chemotherapy.
  5. Previously only received ≤2 line therapy for recurrent and metastatic esophageal squamous cell carcinoma;
  6. Agree to provide archived tumor tissue specimens of primary or metastatic lesion (4 surgical specimens (thickness 5μm) without staining section (anti-removal);6 unstained sections (anti-removal) surgical specimens (thickness 10μm) or fresh tissue samples, if the patient cannot provide, can be included after the investigator's judgment;
  7. There must be at least one measurable lesion conforming to the RECIST V1.1 definition. Tumor lesion located in the area of previous radiotherapy or other local and regional treatment sites is generally not a measurable lesion unless there is definite progression of the lesion or the lesion persists three months after radiotherapy;
  8. Physical fitness ECOG score of 0 or 1;
  9. Toxicity from previous antitumor therapy has returned to ≤1 as defined by NCI-CTCAE V5.0 (except for toxicity that the investigators determined to be of no safety risk, such as hair loss, grade 2 peripheral neurotoxicity, and stabilized hypothyroidism after hormone replacement therapy);
  10. Organ function levels must meet the following requirements and meet the following standards:

    A) Bone marrow function: absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥90×10^9/L, hemoglobin ≥90 g/L; B) Liver function: Total bilirubin TBIL≤1.5×ULN (total bilirubin ≤3×ULN in Subjects with Gilbert's syndrome, liver cancer or liver metastasis), AST and ALT ≤2.5×ULN in patients without liver metastasis, AST and ALT ≤5.0×ULN in patients with liver metastasis; C) Renal function: Creatinine (Cr) ≤1.5×ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula); D) Urine routine / 24-hour protein quantification: qualitative urine protein ≤1+ (if qualitative urine protein ≥2+, 24 hours < 1g can be included); E) Cardiac function: left ventricular ejection fraction ≥50%; F) Coagulation function: International standardized ratio (INR) ≤1.5×ULN, and activated partial thrombin time (APTT) ≤1.5×ULN;

  11. Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence, etc.) with their partner during the trial and for at least 6 months after the last medication;Women of childbearing age must have a negative blood or urine pregnancy test within 7 days prior to the first use of the study drug.

Exclusion Criteria:

  1. Have received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor therapy within 4 weeks prior to the first use of the study drug, except for the following:

    Oral fluorouracil and small molecule targeted drugs were used within 2 weeks before the first administration of the study drug or within 5 half-lives of the drug; The traditional Chinese medicines with anti-tumor indications were within 2 weeks before the first use of the study drug;

  2. Patients with esophageal fistula;
  3. Received an unmarketed clinical investigational drug or treatment within 4 weeks prior to initial use of the investigational drug;
  4. Had major organ surgery (excluding needle biopsy, tracheotomy, gastrostomy, etc.) or had significant trauma within 4 weeks prior to the first use of study drugs, or needed to undergo elective surgery during the trial;
  5. Previous allogeneic hematopoietic stem cell transplantation or organ transplantation;
  6. A history of serious cardiovascular and cerebrovascular diseases, including but not limited to:

    Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, grade iii atrioventricular block, etc; In the resting state, QT interval was prolonged (QTc > 450 msec in men or QTc > 470 msec in women); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 or higher cardio-cerebrovascular events within 6 months prior to the first administration; New York Heart Association (NYHA) heart function grade ≥II heart failure;

  7. Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus, inflammatory bowel disease, etc., except type I diabetes, hypothyroidism that can be controlled only with replacement therapy, and skin diseases that do not require systemic treatment;
  8. Patients with a history of other malignant tumors and signs of recurrence and metastasis within 1 year before the first administration;
  9. Poorly controlled hypertension (systolic blood pressure & GT;150 mmHg or diastolic pressure &gt;100 mmHg);
  10. Pulmonary disease of grade 3 or higher defined by CTCAE V5.0;Patients with past or present interstitial lung disease (ILD);
  11. Cerebral parenchymal or meningeal metastases with clinical symptoms were not suitable for inclusion.
  12. Previous use of anti-EGFR antibody drug therapy;
  13. There are known allergic contraindications to any excipients of SI-B001 or irinotecan;
  14. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection or hepatitis C virus infection;
  15. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, septicemia, etc;'
  16. Pregnant or lactating women;
  17. Persons with mental disorders or poor compliance;
  18. The investigator considers that the subject has a history of other serious systemic diseases or other reasons to be unsuitable for this clinical study.

Sites / Locations

  • Beijing Cancer HostitalRecruiting
  • Anyang Cancer Hospital of Henan ProvinceRecruiting
  • The First Affiliated Hospital of Henan University of Science and TechnologyRecruiting
  • Xuzhou Central HospitalRecruiting
  • Shanxi Cancer HospitalRecruiting
  • Suining Central HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SI-B001 combined with irinotecan

Arm Description

Patients with recurrent metastatic esophageal squamous cell carcinoma who had failed first-line therapy with PD-1(L1) monoclonal antibody plus platinum-based chemotherapy were enrolled.

Outcomes

Primary Outcome Measures

ORR
objective response rate
Optimal combination dose (only IIa)
Optimal combination dose of SI-B001 with irinotecan(only IIa)

Secondary Outcome Measures

PFS
Progression-Free-Survival
DCR
Disease-control rate
DOR
Duration of Response
OS
Overall Survival
TEAE
Treatment Emergent Adverse Events
Cmax
Maximum serum concentration
Tmax
Time to maximum serum concentration
Ctrough
Minimum serum concentration
ADA
anti-SI-B001 antibody

Full Information

First Posted
August 22, 2021
Last Updated
March 14, 2023
Sponsor
Sichuan Baili Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05022654
Brief Title
SI-B001 Combined With Irinotecan in the Treatment of Recurrent Metastatic Esophageal Squamous Cell Carcinoma.
Official Title
Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B001 Combined With Irinotecan in the Treatment of Recurrent and Metastatic Esophageal Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2021 (Actual)
Primary Completion Date
September 1, 2023 (Anticipated)
Study Completion Date
September 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sichuan Baili Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This multi-center, open label Phase II clinical study is performed in patients with relapsed and metastatic esophageal squamous cell carcinoma progressed on prior PD-1/L1 antibody with or without chemotherapy. This study is investigating the safety and efficacy of SI-B001 at optimal combination dose with irinotecan in patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinomas
Keywords
ESCC

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
SI-B001 combined with irinotecan
Arm Type
Experimental
Arm Description
Patients with recurrent metastatic esophageal squamous cell carcinoma who had failed first-line therapy with PD-1(L1) monoclonal antibody plus platinum-based chemotherapy were enrolled.
Intervention Type
Drug
Intervention Name(s)
SI-B001
Intervention Description
Administered by intravenous drip every 2 weeks (Q2W). The first intravenous infusion is 120 min±10min. If the infusion reaction can be tolerated during the first infusion, the subsequent infusion can be completed in 60-120 min.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
The dose of irinotecan was 180mg/m2 Q2W, the infusion method was according to the drug instructions, SI-B001 and irinotecan were used on the same day, and irinotecan was injected after SI-B001 infusion.
Primary Outcome Measure Information:
Title
ORR
Description
objective response rate
Time Frame
Up to approximately 24 months
Title
Optimal combination dose (only IIa)
Description
Optimal combination dose of SI-B001 with irinotecan(only IIa)
Time Frame
Up to approximately 24 months
Secondary Outcome Measure Information:
Title
PFS
Description
Progression-Free-Survival
Time Frame
Up to approximately 24 months
Title
DCR
Description
Disease-control rate
Time Frame
Up to approximately 24 months
Title
DOR
Description
Duration of Response
Time Frame
Up to approximately 24 months
Title
OS
Description
Overall Survival
Time Frame
Up to approximately 24 months
Title
TEAE
Description
Treatment Emergent Adverse Events
Time Frame
Up to approximately 24 months
Title
Cmax
Description
Maximum serum concentration
Time Frame
Up to approximately 24 months
Title
Tmax
Description
Time to maximum serum concentration
Time Frame
Up to approximately 24 months
Title
Ctrough
Description
Minimum serum concentration
Time Frame
Up to approximately 24 months
Title
ADA
Description
anti-SI-B001 antibody
Time Frame
Up to approximately 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Voluntarily sign the informed consent and follow the requirements of the protocol; Male or female, age: ≥18 years and ≤75 years; Expected survival time ≥3 months; Locally advanced esophageal squamous cell carcinoma confirmed histologically or pathologically as recurrent or metastatic or without indications of radical local treatment; Patients who failed or were intolerant to first-line anti-PD-1 (L1) monoclonal antibody plus platinum-based chemotherapy Agree to provide archived tumor tissue specimens of primary or metastatic lesion (4 surgical specimens (thickness 5μm) without staining section (anti-removal);6 unstained sections (anti-removal) surgical specimens (thickness 10μm) or fresh tissue samples, if the patient cannot provide, can be included after the investigator's judgment; There must be at least one measurable lesion conforming to the RECIST V1.1 definition. Tumor lesion located in the area of previous radiotherapy or other local and regional treatment sites is generally not a measurable lesion unless there is definite progression of the lesion or the lesion persists three months after radiotherapy; Physical fitness ECOG score of 0 or 1; Toxicity from previous antitumor therapy has returned to ≤1 as defined by NCI-CTCAE V5.0 (except for toxicity that the investigators determined to be of no safety risk, such as hair loss, grade 2 peripheral neurotoxicity, and stabilized hypothyroidism after hormone replacement therapy); Organ function levels must meet the following requirements and meet the following standards: A) Bone marrow function: absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥90×10^9/L, hemoglobin ≥90 g/L; B) Liver function: Total bilirubin TBIL≤1.5×ULN (total bilirubin ≤3×ULN in Subjects with Gilbert's syndrome, liver cancer or liver metastasis), AST and ALT ≤2.5×ULN in patients without liver metastasis, AST and ALT ≤5.0×ULN in patients with liver metastasis; C) Renal function: Creatinine (Cr) ≤1.5×ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula); D) Urine routine / 24-hour protein quantification: qualitative urine protein ≤1+ (if qualitative urine protein ≥2+, 24 hours < 1g can be included); E) Cardiac function: left ventricular ejection fraction ≥50%; F) Coagulation function: International standardized ratio (INR) ≤1.5×ULN, and activated partial thrombin time (APTT) ≤1.5×ULN; Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence, etc.) with their partner during the trial and for at least 6 months after the last medication;Women of childbearing age must have a negative blood or urine pregnancy test within 7 days prior to the first use of the study drug. Exclusion Criteria: Have received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor therapy within 4 weeks prior to the first use of the study drug, except for the following: Oral fluorouracil and small molecule targeted drugs were used within 2 weeks before the first administration of the study drug or within 5 half-lives of the drug; The traditional Chinese medicines with anti-tumor indications were within 2 weeks before the first use of the study drug; Patients with esophageal fistula; Received an unmarketed clinical investigational drug or treatment within 4 weeks prior to initial use of the investigational drug; Had major organ surgery (excluding needle biopsy, tracheotomy, gastrostomy, etc.) or had significant trauma within 4 weeks prior to the first use of study drugs, or needed to undergo elective surgery during the trial; Previous allogeneic hematopoietic stem cell transplantation or organ transplantation; A history of serious cardiovascular and cerebrovascular diseases, including but not limited to: Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, grade iii atrioventricular block, etc; In the resting state, QT interval was prolonged (QTc > 450 msec in men or QTc > 470 msec in women); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 or higher cardio-cerebrovascular events within 6 months prior to the first administration; New York Heart Association (NYHA) heart function grade ≥II heart failure; Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus, inflammatory bowel disease, etc., except type I diabetes, hypothyroidism that can be controlled only with replacement therapy, and skin diseases that do not require systemic treatment; Patients with a history of other malignant tumors and signs of recurrence and metastasis within 1 year before the first administration; Poorly controlled hypertension (systolic blood pressure & GT;150 mmHg or diastolic pressure &gt;100 mmHg); Pulmonary disease of grade 3 or higher defined by CTCAE V5.0;Patients with past or present interstitial lung disease (ILD); Cerebral parenchymal or meningeal metastases with clinical symptoms were not suitable for inclusion. Previous use of anti-EGFR antibody drug therapy; There are known allergic contraindications to any excipients of SI-B001 or irinotecan; Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection or hepatitis C virus infection; Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, septicemia, etc;' Pregnant or lactating women; Persons with mental disorders or poor compliance; The investigator considers that the subject has a history of other serious systemic diseases or other reasons to be unsuitable for this clinical study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hai Zhu
Phone
+8613980051002
Email
zhuhai@baili-pharm.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sa Xiao
Phone
+8615013238943
Email
xiaosa@baili-pharm.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lin Shen
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Cancer Hostital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lin Shen
Phone
01088196561
Email
doctorshenlin@sina.cn
Facility Name
Anyang Cancer Hospital of Henan Province
City
Anyang
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Junsheng Wang
Facility Name
The First Affiliated Hospital of Henan University of Science and Technology
City
Luoyang
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shegan Gao
Facility Name
Xuzhou Central Hospital
City
Xuzhou
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuan Yuan
Facility Name
Shanxi Cancer Hospital
City
Taiyuan
State/Province
Shanxi
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mudan Yang
Facility Name
Suining Central Hospital
City
Suining
State/Province
Sichuan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Na Li

12. IPD Sharing Statement

Learn more about this trial

SI-B001 Combined With Irinotecan in the Treatment of Recurrent Metastatic Esophageal Squamous Cell Carcinoma.

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