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Neoadjuvant Treatment of Cadonilimab Combined Albumin-paclitaxel, Cisplatin and Fluorouracil for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

Primary Purpose

The Efficacy and Safety of Therapy Efficacy for Locally Advanced ESCC

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Cadonilimab Combined Albumin-paclitaxel, Cisplatin and Fluorouracil
Sponsored by
Weijia Fang, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for The Efficacy and Safety of Therapy Efficacy for Locally Advanced ESCC

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants who have given their consent and signed an informed consent form, are willing and able to comply with the study visits, treatment, laboratory tests, and other trial procedures. Patients with a pathological diagnosis of (thoracic) esophageal squamous cell carcinoma. Age between 18 and 75 years (inclusive), both male and female. Locally advanced esophageal squamous cell carcinoma without suspicious cervical lymph node metastasis and distant metastasis (cT1N1-3M0 or cT2-3N0-3M0, AJCC 8th edition). Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. No prior systemic treatment for esophageal cancer (including chemotherapy, targeted therapy, immune checkpoint inhibitors such as anti-PD-1 or PD-L1 antibodies, anti-CTLA-4 antibodies, etc.). Planned surgical treatment after completion of neoadjuvant therapy. Expected survival time of at least 6 months. Clearly measurable lesions that meet the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Adequate organ function based on laboratory values obtained during the screening period, including: 1) Hematology: no blood transfusions or blood products within 14 days, no use of G-CSF or other hematopoietic growth factors for correction, white blood cell count (WBC) ≥ 3.0 × 109/L, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 75 × 109/L, hemoglobin (Hgb) ≥ 9 g/dL. 2) Blood chemistry: serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase or alanine aminotransferase ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastasis), serum creatinine ≤ 1.5 × ULN. 3) Coagulation function: prothrombin time (PT), international normalized ratio (INR) ≤ 1.5 × ULN. 4) Cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%. 11. Female participants of childbearing potential must have a negative serum pregnancy test within 3 days before starting study drug and agree to use a medically accepted highly effective method of contraception (such as an intrauterine device, contraceptive pills, or condoms) during the study period and within 3 months after the last dose of study drug. Male participants with partners of childbearing potential must have undergone surgical sterilization or agree to use an effective method of contraception during the study period and within 3 months after the last dose of study drug. Exclusion Criteria: History of or concurrent active malignancy other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer or other malignancy with no evidence of disease for at least 5 years. Active bleeding within 3 months; a history of arterial or venous thrombotic events within 6 months, such as stroke (including transient ischemic attack), deep vein thrombosis, and pulmonary embolism; known inherited or acquired bleeding diathesis (e.g., coagulation factor deficiencies) or thrombotic disorders, such as patients with hemophilia; current or recent (within 10 days before the start of the study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (allowed prophylactic use of low-dose aspirin and low-molecular-weight heparin); major surgery (excluding biopsy) within 4 weeks before starting study drug treatment or the surgical incision has not fully healed; current or recent (within 10 days before the start of the study treatment) use of aspirin (> 325 mg/day [maximum antiplatelet dose]) or other nonsteroidal anti-inflammatory drugs, dual antiplatelet therapy, clopidogrel, prasugrel, ticagrelor, or cilostazol. The patient has received systemic treatment, surgery, or radiotherapy for esophageal cancer, including immunotherapy such as anti-PD-1 or PD-L1 antibodies, anti-CTLA-4 antibodies, targeted therapy, or chemotherapy. The patient has used systemic corticosteroids or other systemic immunosuppressive drugs within 2 weeks before treatment, or is expected to use systemic immunosuppressive drugs during the trial. The use of inhaled glucocorticoids or physiological replacement doses of glucocorticoids is allowed. The patient has active autoimmune diseases. Patients with type 1 diabetes, hypothyroidism requiring replacement therapy only, skin diseases (such as vitiligo, psoriasis, or alopecia) that do not require systemic treatment or are not expected to recur without external triggering factors can be included in the trial. The patient has known active tuberculosis, is receiving anti-tuberculosis treatment, or has received anti-tuberculosis treatment within 1 year prior to the first dose. The patient has severe, uncontrolled systemic diseases, such as refractory hypertension, severe active infection, etc. The patient has known human immunodeficiency virus (HIV) infection or is known to be HIV-seropositive. Untreated chronic hepatitis B or active carriers of hepatitis B virus (HBV) (HBV DNA >500 IU/mL) or active carriers of HCV detectable by HCV RNA. Note: Inactive carriers of hepatitis B surface antigen (HBsAg) or stable patients with treated chronic hepatitis B (HBV DNA < 500 IU/mL) can be included in the study. History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, or symptomatic interstitial lung disease, or active pneumonia detected by chest CT scan within 4 weeks prior to initial drug treatment in the study. Known symptomatic, untreated, or progressively advancing central nervous system (CNS) or leptomeningeal metastases. Known allergy to any investigational drug or excipient. Participation in other drug clinical trials within 4 weeks before enrollment. Breastfeeding women. As judged by the investigator, the patient has other factors that may affect the study results or may cause premature termination of the study, such as alcoholism, drug abuse, other serious illnesses (including mental illness) requiring concomitant treatment, significant laboratory abnormalities, or family or social factors that may affect the patient's safety.

Sites / Locations

  • Lulu LiuRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AK104+cisplatin+albumin paclitaxel+fluorouracil

Arm Description

AK104 (10 mg/kg d1), in combination with cisplatin (20 mg/m2 on d1-3) and albumin paclitaxel (100mg/m2 on d1,d8), fluorouracil (600 mg/m2 on d1-5) Q3W, intravenously

Outcomes

Primary Outcome Measures

pathologic complete response (pCR) of the patients' resected tumors
PCR is defined as pT0N0M0

Secondary Outcome Measures

Major pathologic response (MPR)
MPR is defined as viable tumor comprised ≤ 10% of resected tumor specimens.
Disease Free Survival (DFS)
Percentage of Participants With DFS, as Assessed by RECIST 1.1. DFS is defined as the time from randomization to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
pathological downstaging rate
The rate of patients with reduced pathological stage after neoadjuvant therapy
R0 resection rate
The rate of patients with R0 resection after neoadjuvant therapy

Full Information

First Posted
May 7, 2023
Last Updated
August 3, 2023
Sponsor
Weijia Fang, MD
Collaborators
Akeso Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05947201
Brief Title
Neoadjuvant Treatment of Cadonilimab Combined Albumin-paclitaxel, Cisplatin and Fluorouracil for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma
Official Title
Neoadjuvant Treatment of Cadonilimab Combined Albumin-paclitaxel, Cisplatin and Fluorouracil for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma:A Single-Arm Phase 2 Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 8, 2023 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
October 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Weijia Fang, MD
Collaborators
Akeso Pharmaceuticals, Inc.

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
No

5. Study Description

Brief Summary
This is a single-arm clinical study to evaluate the efficacy and safety of Cadonilimab in combination with preoperative chemotherapy for locally advanced esophageal squamous cell carcinoma Locally Advanced Esophageal Squamous Cell Carcinoma
Detailed Description
Esophageal cancer is the eighth most lethal tumor and the sixth leading cause of cancer-related deaths worldwide. Esophageal squamous cell carcinoma accounts for up to 95% of the pathological types and threatens the health of chinese residents. Investigator designed a single-arm, open-label, phase II trial and the purpose of this study is to observe and evaluate the efficacy and safety of Cadonilimab combined with preoperative chemotherapy for locally advanced esophageal squamous cell carcinoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
The Efficacy and Safety of Therapy Efficacy for Locally Advanced ESCC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Patients fulfilling Eligibility Criteria will be included in our study. ESCC participants in this study will be given intravenous administration of AK104 (10 mg/kg d1) combined with cisplatin (20 mg/m2 on d1-3) and albumin paclitaxel (100mg/m2 on d1, d8), fluorouracil (600 mg/m2 on d1-5) every three weeks for a cycle of treatment, which will be conducted two or three cycles, and radical surgery within 4-6 weeks after the last administration. Treatments will be administrated until disease progression, unacceptable adverse events (AE), concomitant diseases that hinder continued treatment.
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AK104+cisplatin+albumin paclitaxel+fluorouracil
Arm Type
Experimental
Arm Description
AK104 (10 mg/kg d1), in combination with cisplatin (20 mg/m2 on d1-3) and albumin paclitaxel (100mg/m2 on d1,d8), fluorouracil (600 mg/m2 on d1-5) Q3W, intravenously
Intervention Type
Drug
Intervention Name(s)
Cadonilimab Combined Albumin-paclitaxel, Cisplatin and Fluorouracil
Other Intervention Name(s)
rutine
Intervention Description
If the addition of Cadonilimab to neoadjuvant chemotherapy further improve the efficiency for locally advanced esophageal squamous cell carcinoma
Primary Outcome Measure Information:
Title
pathologic complete response (pCR) of the patients' resected tumors
Description
PCR is defined as pT0N0M0
Time Frame
1 month after resection
Secondary Outcome Measure Information:
Title
Major pathologic response (MPR)
Description
MPR is defined as viable tumor comprised ≤ 10% of resected tumor specimens.
Time Frame
1 month after resection
Title
Disease Free Survival (DFS)
Description
Percentage of Participants With DFS, as Assessed by RECIST 1.1. DFS is defined as the time from randomization to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.
Time Frame
3 and 5 years
Title
Overall Survival (OS)
Description
OS is defined as the time from randomization to death due to any cause.
Time Frame
3 and 5 years
Title
pathological downstaging rate
Description
The rate of patients with reduced pathological stage after neoadjuvant therapy
Time Frame
1 month after resection
Title
R0 resection rate
Description
The rate of patients with R0 resection after neoadjuvant therapy
Time Frame
1 month after resection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants who have given their consent and signed an informed consent form, are willing and able to comply with the study visits, treatment, laboratory tests, and other trial procedures. Patients with a pathological diagnosis of (thoracic) esophageal squamous cell carcinoma. Age between 18 and 75 years (inclusive), both male and female. Locally advanced esophageal squamous cell carcinoma without suspicious cervical lymph node metastasis and distant metastasis (cT1N1-3M0 or cT2-3N0-3M0, AJCC 8th edition). Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. No prior systemic treatment for esophageal cancer (including chemotherapy, targeted therapy, immune checkpoint inhibitors such as anti-PD-1 or PD-L1 antibodies, anti-CTLA-4 antibodies, etc.). Planned surgical treatment after completion of neoadjuvant therapy. Expected survival time of at least 6 months. Clearly measurable lesions that meet the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Adequate organ function based on laboratory values obtained during the screening period, including: 1) Hematology: no blood transfusions or blood products within 14 days, no use of G-CSF or other hematopoietic growth factors for correction, white blood cell count (WBC) ≥ 3.0 × 109/L, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 75 × 109/L, hemoglobin (Hgb) ≥ 9 g/dL. 2) Blood chemistry: serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase or alanine aminotransferase ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastasis), serum creatinine ≤ 1.5 × ULN. 3) Coagulation function: prothrombin time (PT), international normalized ratio (INR) ≤ 1.5 × ULN. 4) Cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%. 11. Female participants of childbearing potential must have a negative serum pregnancy test within 3 days before starting study drug and agree to use a medically accepted highly effective method of contraception (such as an intrauterine device, contraceptive pills, or condoms) during the study period and within 3 months after the last dose of study drug. Male participants with partners of childbearing potential must have undergone surgical sterilization or agree to use an effective method of contraception during the study period and within 3 months after the last dose of study drug. Exclusion Criteria: History of or concurrent active malignancy other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer or other malignancy with no evidence of disease for at least 5 years. Active bleeding within 3 months; a history of arterial or venous thrombotic events within 6 months, such as stroke (including transient ischemic attack), deep vein thrombosis, and pulmonary embolism; known inherited or acquired bleeding diathesis (e.g., coagulation factor deficiencies) or thrombotic disorders, such as patients with hemophilia; current or recent (within 10 days before the start of the study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (allowed prophylactic use of low-dose aspirin and low-molecular-weight heparin); major surgery (excluding biopsy) within 4 weeks before starting study drug treatment or the surgical incision has not fully healed; current or recent (within 10 days before the start of the study treatment) use of aspirin (> 325 mg/day [maximum antiplatelet dose]) or other nonsteroidal anti-inflammatory drugs, dual antiplatelet therapy, clopidogrel, prasugrel, ticagrelor, or cilostazol. The patient has received systemic treatment, surgery, or radiotherapy for esophageal cancer, including immunotherapy such as anti-PD-1 or PD-L1 antibodies, anti-CTLA-4 antibodies, targeted therapy, or chemotherapy. The patient has used systemic corticosteroids or other systemic immunosuppressive drugs within 2 weeks before treatment, or is expected to use systemic immunosuppressive drugs during the trial. The use of inhaled glucocorticoids or physiological replacement doses of glucocorticoids is allowed. The patient has active autoimmune diseases. Patients with type 1 diabetes, hypothyroidism requiring replacement therapy only, skin diseases (such as vitiligo, psoriasis, or alopecia) that do not require systemic treatment or are not expected to recur without external triggering factors can be included in the trial. The patient has known active tuberculosis, is receiving anti-tuberculosis treatment, or has received anti-tuberculosis treatment within 1 year prior to the first dose. The patient has severe, uncontrolled systemic diseases, such as refractory hypertension, severe active infection, etc. The patient has known human immunodeficiency virus (HIV) infection or is known to be HIV-seropositive. Untreated chronic hepatitis B or active carriers of hepatitis B virus (HBV) (HBV DNA >500 IU/mL) or active carriers of HCV detectable by HCV RNA. Note: Inactive carriers of hepatitis B surface antigen (HBsAg) or stable patients with treated chronic hepatitis B (HBV DNA < 500 IU/mL) can be included in the study. History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, or symptomatic interstitial lung disease, or active pneumonia detected by chest CT scan within 4 weeks prior to initial drug treatment in the study. Known symptomatic, untreated, or progressively advancing central nervous system (CNS) or leptomeningeal metastases. Known allergy to any investigational drug or excipient. Participation in other drug clinical trials within 4 weeks before enrollment. Breastfeeding women. As judged by the investigator, the patient has other factors that may affect the study results or may cause premature termination of the study, such as alcoholism, drug abuse, other serious illnesses (including mental illness) requiring concomitant treatment, significant laboratory abnormalities, or family or social factors that may affect the patient's safety.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lu lu Liu, M.D.
Phone
0571-87237587
Email
liululu2001@zju.edu.cn
Facility Information:
Facility Name
Lulu Liu
City
Hanzhou
State/Province
Zhejiang
ZIP/Postal Code
0571
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lu lu Liu, M.D.
Phone
0571-87237587
Email
liululu2001@zju.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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Neoadjuvant Treatment of Cadonilimab Combined Albumin-paclitaxel, Cisplatin and Fluorouracil for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

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