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Candonilimab (AK104) Plus Preoperative Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)

Primary Purpose

Esophageal Squamous Cell Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
AK104, nab-paclitaxel, carboplatin
Sponsored by
The First Affiliated Hospital of Zhengzhou 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 AK104, preoperative chemotherapy, surgery

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Voluntarily signing a written informed consent form; Males or females aged ≥ 18 to ≤ 70 years; ECOG score 0-1; Pathologically diagnosed thoracic esophageal squamous cell carcinoma; No distant metastasis after imaging examination, and esophageal cancer can be resected or potentially resectable with stage cT1b-cT2N+M0 or cT3-cT4a anyN M0 or cT2N0M0 high-risk (lymphovascular invasion or tumor ≥3 cm or hypo-differentiation) (AJCC 8th edition cTNM stage); Not received prior antitumor therapy (surgery, radiotherapy, chemotherapy, immunotherapy, etc. for esophageal cancer); Life expectancy is greater than 6 months; At least one measurable tumor lesion per RECIST v1.1; Major organ functions are adequate; Exclusion Criteria: Patient has received previous antitumor therapy (chemotherapy, radiation, surgery or immunotherapy); Cervical or thoracic esophageal cancer is < 5 cm from the cricopharyngeal muscle; Patients are or are expected to be at significant risk of esophageal perforation, fistula, and major bleeding; Imaging during the screening period showed that the tumor surrounded or invaded important blood vessels or organs (such as the heart and pericardium, trachea, aorta, superior vena cava, etc.) or there was obvious necrosis or cavity, and the investigator determined that entering the study would cause bleeding risk; participants at risk of developing oesophageal or oesophageal fistula; Patients with a history of other malignant diseases in the last 5 years,unless complete resolution or no additional treatment is required (exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer or prostate, cervix, or breast carcinoma in situ); Pregnant or nursing women; Patients with known or suspected active autoimmune disease; Patients with a history of myocarditis, cardiomyopathy, malignant arrhythmias; Other patients are not eligible for enrollment assessed by investigators;

Sites / Locations

  • Anyang Cancer Hospital
  • Feng Wang

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AK104 plus nab-paclitaxel and carboplatin

Arm Description

In the induction period, AK104 (10mg/kg, iv, Q2W) is given for one cycle; and then AK104 (10mg/kg, iv, Q3W) is combined with nab-paclitaxel (130mg/m2 ivgtt d1,d8, Q3W) and carboplatin ((AUC=5) d1,Q3W) for 2 cycles; After R0 surgery, AK104 (10mg/kg, iv, Q3W) is given as adjuvant therapy for up to 12 months for those who do not achieve pCR.

Outcomes

Primary Outcome Measures

pCR
Pathological complete response

Secondary Outcome Measures

MPR
Major pathologic response
R0 resection rate
R0 resection rate
Downstaging rate
Downstaging rate
DFS
Disease-free survival
OS
Overall survival
AE
Adverse event

Full Information

First Posted
June 1, 2023
Last Updated
June 1, 2023
Sponsor
The First Affiliated Hospital of Zhengzhou University
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1. Study Identification

Unique Protocol Identification Number
NCT05896787
Brief Title
Candonilimab (AK104) Plus Preoperative Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Official Title
A Phase II Study of Candonilimab (AK104) Combined With Preoperative Chemotherapy in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 1, 2023 (Anticipated)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
August 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of Zhengzhou University

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 is a prospective, single-arm, open-label,multi-center, phase II study, aiming to evaluate the efficacy and safety of AK104 combined with preoperative chemotherapy in patients with locally advanced ESCC.
Detailed Description
Eligible patients first receive AK104 (10mg/kg, iv, Q2W) for one cycle in the induction period, and then patients receive AK104 (10mg/kg, iv, Q3W) combined with nab-paclitaxel (130mg/m2 ivgtt d1,d8, Q3W) and carboplatin ((AUC=5) d1,Q3W) for 2 cycles. After neoadjuvant therapy of 3 cycles, patient will undergo preoperative evaluation. For patients who can be performed for R0 surgery, surgery wil be performed in 4 to 6 weeks. Patients who do not achieve Pathological complete response (pCR) will receive AK104 (10mg/kg, iv, Q3W) as adjuvant therapy until disease progression or intolerable toxicity for up to 12 months. Patients who achieve pCR after surgery will be enrolled in observational follow-up.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma
Keywords
AK104, preoperative chemotherapy, surgery

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
AK104 plus nab-paclitaxel and carboplatin
Arm Type
Experimental
Arm Description
In the induction period, AK104 (10mg/kg, iv, Q2W) is given for one cycle; and then AK104 (10mg/kg, iv, Q3W) is combined with nab-paclitaxel (130mg/m2 ivgtt d1,d8, Q3W) and carboplatin ((AUC=5) d1,Q3W) for 2 cycles; After R0 surgery, AK104 (10mg/kg, iv, Q3W) is given as adjuvant therapy for up to 12 months for those who do not achieve pCR.
Intervention Type
Drug
Intervention Name(s)
AK104, nab-paclitaxel, carboplatin
Other Intervention Name(s)
Candonilimab,Preoperative Chemotherapy
Intervention Description
AK104 plus nab-paclitaxel and carboplatin as neoadjuvant therapy,and AK104 as adjuvant therapy for those who do not achieve pCR;
Primary Outcome Measure Information:
Title
pCR
Description
Pathological complete response
Time Frame
up to 2 years
Secondary Outcome Measure Information:
Title
MPR
Description
Major pathologic response
Time Frame
up to 2 years
Title
R0 resection rate
Description
R0 resection rate
Time Frame
up to 2 years
Title
Downstaging rate
Description
Downstaging rate
Time Frame
up to 2 years
Title
DFS
Description
Disease-free survival
Time Frame
up to 2 years
Title
OS
Description
Overall survival
Time Frame
up to 2 years
Title
AE
Description
Adverse event
Time Frame
up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Voluntarily signing a written informed consent form; Males or females aged ≥ 18 to ≤ 70 years; ECOG score 0-1; Pathologically diagnosed thoracic esophageal squamous cell carcinoma; No distant metastasis after imaging examination, and esophageal cancer can be resected or potentially resectable with stage cT1b-cT2N+M0 or cT3-cT4a anyN M0 or cT2N0M0 high-risk (lymphovascular invasion or tumor ≥3 cm or hypo-differentiation) (AJCC 8th edition cTNM stage); Not received prior antitumor therapy (surgery, radiotherapy, chemotherapy, immunotherapy, etc. for esophageal cancer); Life expectancy is greater than 6 months; At least one measurable tumor lesion per RECIST v1.1; Major organ functions are adequate; Exclusion Criteria: Patient has received previous antitumor therapy (chemotherapy, radiation, surgery or immunotherapy); Cervical or thoracic esophageal cancer is < 5 cm from the cricopharyngeal muscle; Patients are or are expected to be at significant risk of esophageal perforation, fistula, and major bleeding; Imaging during the screening period showed that the tumor surrounded or invaded important blood vessels or organs (such as the heart and pericardium, trachea, aorta, superior vena cava, etc.) or there was obvious necrosis or cavity, and the investigator determined that entering the study would cause bleeding risk; participants at risk of developing oesophageal or oesophageal fistula; Patients with a history of other malignant diseases in the last 5 years,unless complete resolution or no additional treatment is required (exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer or prostate, cervix, or breast carcinoma in situ); Pregnant or nursing women; Patients with known or suspected active autoimmune disease; Patients with a history of myocarditis, cardiomyopathy, malignant arrhythmias; Other patients are not eligible for enrollment assessed by investigators;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Feng Wang
Phone
13938244776
Email
fengw010@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Feng Wang
Organizational Affiliation
The First Affiliated Hospital of Zhengzhou University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Anyang Cancer Hospital
City
Anyang
State/Province
Henan
ZIP/Postal Code
450052
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anlin Hao
Facility Name
Feng Wang
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450052
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Feng Wang

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Candonilimab (AK104) Plus Preoperative Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)

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