search
Back to results

Camrelizumab Combined With Neoadjuvant Concurrent Chemoradiotherapy for Resectable Locally Advanced ESCC(NICE-RT)

Primary Purpose

Esophageal Squamous Cell Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Chemotherapy (nab-paclitaxel AUC=2 and carboplatin 80mg/m2),Immunotherapy (camrelizumab 200mg)、Radiotherapy(primary lesion and adjacent lymph nodes 41.4Gy, distant lymph node 0.5Gy*4)
Sponsored by
Shanghai Chest Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma

Eligibility Criteria

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

Inclusion Criteria: Informed consent has been signed. In age from 18 to 75. Thoracic esophageal squamous cell carcinoma confirmed by histology or cytology, which is classified as cT1b-4aN2-3M0 or M1 (only for supraclavicular lymph node metastasis), accompanied by lymph node metastasis (CT shows that the short diameter of the lymph node is greater than 1cm, the lymph node near the recurrent laryngeal nerve is greater than 8mm, the lymph node in the left upper abdominal region of the stomach is greater than 8mm, and PET-CT indicates positive). At least one metastatic lymph node is more than or equal to 5cm from the primary lesion. Have not received any anti-tumor treatment for esophageal cancer in the past, including radiotherapy, chemotherapy, surgery, etc. The investigator assessed that lesion can be removed surgically. At least one measurable lesion (according to RECIST 1.1) ECOG PS: 0~1. Weight loss<10% within 3 months, PG-SGA score<8. Has sufficient organ function within 28 days before the first administration, (1) Blood routine: WBC≥3.0×109/L; ANC≥1.5×109/L; PLT≥50×109/L; HGB≥90 g/L (2) Liver function: AST≤5.0×ULN; ALT≤5.0×ULN; TBIL≤2.0×ULN (3) Renal function: Cr≤1.5×ULN or CrCl ≥60 mL/min (4) Coagulation function: INR≤1.5; APTT≤1.5×ULN (5)Women of childbearing age must take contraceptive measures within 3 months from the first dose to the last use of the study drug. Exclusion Criteria: 1.Pathological type and stage Pathology indicates that it is mixed squamous cell carcinoma (including adenosquamous carcinoma, squamous cell carcinoma, small cell carcinoma, carcinosarcoma, sarcomatoid carcinoma, etc.) Non resectable or metastatic esophageal cancer 2. Medical history and complications Subjects with any known active autoimmune disease (subjects who have stable clinical symptoms and do not need systematic use of immunosuppressants, such as type I diabetes and hypothyroidism that only need hormone treatment, and skin diseases that do not need systematic treatment can be included). Subjects who have any complications requiring systemic treatment with glucocorticoids such as prednisone (>10mg/day) or who have used immunosuppressive drugs within 14 days before the first administration (subjects who do not have active autoimmune diseases, inhale or locally use glucocorticoids, and who use prednisone (>10mg/day) for hormone replacement treatment of adrenal insufficiency can be included in the group). Subjects have received tumor vaccine or other immune activated anti-tumor drugs (such as interferon, interleukin, thymosin or immunocyte therapy) within 1 month before the first administration. The subject is participating in other clinical trials or has received drug intervention from other clinical trials within 4 weeks before the first administration. Subjects had received surgery or radiotherapy>30Gy within 4 weeks before the first administration. Subjects with other malignant tumors that need to be treated (subjects with skin basal cell carcinoma, skin squamous cell carcinoma, breast cancer in situ or cervical cancer in situ that have received radical treatment and do not need other treatment can be included) Subjects have suffered from serious cardiovascular diseases in the past: myocardial ischemia or myocardial infarction above Grade II, arrhythmia under poor control (including QTc interval ≥ 480 ms); Grade III-IV cardiac insufficiency; Color Doppler echocardiography showed that left ventricular ejection fraction (LVEF) was less than 50%. Subjects have known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. Subjects received live vaccine within 30 days before the first administration. 3. Laboratory inspection The subject's serum is HIV positive Active hepatitis B (HbsAg positive and HBV-DNA ≥ 103 copies/mL) or active hepatitis C (HCV antibody positive and HCV-DNA positive, requiring antiviral treatment at the same time). 4. Allergies and adverse drug reactions should be excluded Presence of allergy or hypersensitivity to monoclonal antibodies Allergy or intolerance during infusion 5. Diseases or abnormal laboratory indicators that the investigator believes will affect the research results or are not in line with the interests of the subject should be excluded.

Sites / Locations

  • Shanghai Chest Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Immunotherapy combined with Chemoradiotherapy

Arm Description

A:Chemotherapy: nab-paclitaxel (80mg/m2), carboplatin (AUC=2),on day 1,8,15,22,29; B:Immunotherapy: camrelizumab (200mg),IV on days 5 and 26; C:Radiotherapy: Primary lesion and adjacent lymph nodes: 41.4Gy, 1.8Gy/23f; Abscopal lymph node 2Gy, 0.5Gy/4f. D:Ivor-Lewis or McKeown esophagectomy The participants will receive preoperative A+B+C. 4-6 weeks after completion of preoperative therapy ,D will be performed if there is no contraindication.

Outcomes

Primary Outcome Measures

Safety(The rates of grade 3 and higher-grade treatment-related adverse events)
Incidence of adverse events using CTCAE 4.03;grade 3 treatment-related adverse events and higher-grade adverse event will be reported
pCR
pathological complete response (pCR) is defined as disappearance of all invasive cancer after completion of neoadjuvant chemotherapy

Secondary Outcome Measures

MPR
major pathologic response (MPR) is defined as residual viable tumor of less than or equal to 10%
ORR
objective response rate (ORR) is defined as the proportion of patients with a complete response(CR) or partial response(PR) to treatment according to RECIST v1.1
EFS
event-free survival (EFS) is defined as the time after treatment that a group of people in a clinical trial has not had cancer come back or get worse
OS
overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence

Full Information

First Posted
November 24, 2022
Last Updated
December 6, 2022
Sponsor
Shanghai Chest Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05650216
Brief Title
Camrelizumab Combined With Neoadjuvant Concurrent Chemoradiotherapy for Resectable Locally Advanced ESCC(NICE-RT)
Official Title
A Single-arm,Single-center,Phase II Trial of Camrelizumab Combined With Neoadjuvant Concurrent Chemoradiotherapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma(NICE-RT)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 25, 2022 (Anticipated)
Primary Completion Date
December 25, 2023 (Anticipated)
Study Completion Date
December 25, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Chest Hospital

4. Oversight

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

5. Study Description

Brief Summary
NICE-RT study is a "safety run-in" and phase II trial evaluating the safety and efficacy of Camrelizumab combined with Nab-paclitaxel and Carboplatin and Radiotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma.
Detailed Description
Considering that immunotherapy combined with concurrent chemoradiotherapy may have unknown AEs, in order to explore the safety and tolerability of the regimen of camrelizumab combined with nab-paclitaxel and carboplatin and radiotherapy, this study set up an initial "safety run-in" phase. 10 patients will be firstly enrolled, and treatment-related adverse reactions(TRAEs)and surgical complications will be observed at the same time. If the completion rate of neoadjuvant therapy and surgery is greater than 80%, rate of 30-day major complication is less than 20%,and no death, it will continue to enroll 40 patients to explore the efficacy and safety of the regimen. If the completion rate of neoadjuvant therapy and surgery is less than 80%, the MDT will determine whether the study move forward. If treatment related death is more than 1 patients, the study will be terminated.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Immunotherapy combined with Chemoradiotherapy
Arm Type
Experimental
Arm Description
A:Chemotherapy: nab-paclitaxel (80mg/m2), carboplatin (AUC=2),on day 1,8,15,22,29; B:Immunotherapy: camrelizumab (200mg),IV on days 5 and 26; C:Radiotherapy: Primary lesion and adjacent lymph nodes: 41.4Gy, 1.8Gy/23f; Abscopal lymph node 2Gy, 0.5Gy/4f. D:Ivor-Lewis or McKeown esophagectomy The participants will receive preoperative A+B+C. 4-6 weeks after completion of preoperative therapy ,D will be performed if there is no contraindication.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy (nab-paclitaxel AUC=2 and carboplatin 80mg/m2),Immunotherapy (camrelizumab 200mg)、Radiotherapy(primary lesion and adjacent lymph nodes 41.4Gy, distant lymph node 0.5Gy*4)
Other Intervention Name(s)
Camrelizumab: ai rui ka, SHR-1210; Nab-paclitaxel: ai yue
Intervention Description
Neoadjuvant treatment period: Radiotherapy: Primary lesions and adjacent lymph nodes: The mode of involved field irradiation (IFI) is adopted, no preventive radiation is given. The total dose is 41.4Gy, 1.8Gy/23f. Distal lymph nodes ≥ 5cm away from the primary lesion: low-dose radiotherapy with a total dose of 4Gy, 0.5Gy/8f, Day1 to Day4, Day22 to Day25. Chemotherapy: Carboplatin(AUC=2), Nab-paclitaxel(80mg/m2), Day1/8/15/22/29. Immunotherapy: Camrelizumab(200mg, Day5, Day26). Perioperative period: Undergo surgery within 4-6 weeks after neoadjuvant therapy Adjuvant treatment period: Camrelizumab: (200mg, Q3W),continued for up to 1 years,until PD or intolerable toxicity.
Primary Outcome Measure Information:
Title
Safety(The rates of grade 3 and higher-grade treatment-related adverse events)
Description
Incidence of adverse events using CTCAE 4.03;grade 3 treatment-related adverse events and higher-grade adverse event will be reported
Time Frame
From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose
Title
pCR
Description
pathological complete response (pCR) is defined as disappearance of all invasive cancer after completion of neoadjuvant chemotherapy
Time Frame
12 months
Secondary Outcome Measure Information:
Title
MPR
Description
major pathologic response (MPR) is defined as residual viable tumor of less than or equal to 10%
Time Frame
12 months
Title
ORR
Description
objective response rate (ORR) is defined as the proportion of patients with a complete response(CR) or partial response(PR) to treatment according to RECIST v1.1
Time Frame
12 months
Title
EFS
Description
event-free survival (EFS) is defined as the time after treatment that a group of people in a clinical trial has not had cancer come back or get worse
Time Frame
12 months
Title
OS
Description
overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence
Time Frame
12 months

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: Informed consent has been signed. In age from 18 to 75. Thoracic esophageal squamous cell carcinoma confirmed by histology or cytology, which is classified as cT1b-4aN2-3M0 or M1 (only for supraclavicular lymph node metastasis), accompanied by lymph node metastasis (CT shows that the short diameter of the lymph node is greater than 1cm, the lymph node near the recurrent laryngeal nerve is greater than 8mm, the lymph node in the left upper abdominal region of the stomach is greater than 8mm, and PET-CT indicates positive). At least one metastatic lymph node is more than or equal to 5cm from the primary lesion. Have not received any anti-tumor treatment for esophageal cancer in the past, including radiotherapy, chemotherapy, surgery, etc. The investigator assessed that lesion can be removed surgically. At least one measurable lesion (according to RECIST 1.1) ECOG PS: 0~1. Weight loss<10% within 3 months, PG-SGA score<8. Has sufficient organ function within 28 days before the first administration, (1) Blood routine: WBC≥3.0×109/L; ANC≥1.5×109/L; PLT≥50×109/L; HGB≥90 g/L (2) Liver function: AST≤5.0×ULN; ALT≤5.0×ULN; TBIL≤2.0×ULN (3) Renal function: Cr≤1.5×ULN or CrCl ≥60 mL/min (4) Coagulation function: INR≤1.5; APTT≤1.5×ULN (5)Women of childbearing age must take contraceptive measures within 3 months from the first dose to the last use of the study drug. Exclusion Criteria: 1.Pathological type and stage Pathology indicates that it is mixed squamous cell carcinoma (including adenosquamous carcinoma, squamous cell carcinoma, small cell carcinoma, carcinosarcoma, sarcomatoid carcinoma, etc.) Non resectable or metastatic esophageal cancer 2. Medical history and complications Subjects with any known active autoimmune disease (subjects who have stable clinical symptoms and do not need systematic use of immunosuppressants, such as type I diabetes and hypothyroidism that only need hormone treatment, and skin diseases that do not need systematic treatment can be included). Subjects who have any complications requiring systemic treatment with glucocorticoids such as prednisone (>10mg/day) or who have used immunosuppressive drugs within 14 days before the first administration (subjects who do not have active autoimmune diseases, inhale or locally use glucocorticoids, and who use prednisone (>10mg/day) for hormone replacement treatment of adrenal insufficiency can be included in the group). Subjects have received tumor vaccine or other immune activated anti-tumor drugs (such as interferon, interleukin, thymosin or immunocyte therapy) within 1 month before the first administration. The subject is participating in other clinical trials or has received drug intervention from other clinical trials within 4 weeks before the first administration. Subjects had received surgery or radiotherapy>30Gy within 4 weeks before the first administration. Subjects with other malignant tumors that need to be treated (subjects with skin basal cell carcinoma, skin squamous cell carcinoma, breast cancer in situ or cervical cancer in situ that have received radical treatment and do not need other treatment can be included) Subjects have suffered from serious cardiovascular diseases in the past: myocardial ischemia or myocardial infarction above Grade II, arrhythmia under poor control (including QTc interval ≥ 480 ms); Grade III-IV cardiac insufficiency; Color Doppler echocardiography showed that left ventricular ejection fraction (LVEF) was less than 50%. Subjects have known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. Subjects received live vaccine within 30 days before the first administration. 3. Laboratory inspection The subject's serum is HIV positive Active hepatitis B (HbsAg positive and HBV-DNA ≥ 103 copies/mL) or active hepatitis C (HCV antibody positive and HCV-DNA positive, requiring antiviral treatment at the same time). 4. Allergies and adverse drug reactions should be excluded Presence of allergy or hypersensitivity to monoclonal antibodies Allergy or intolerance during infusion 5. Diseases or abnormal laboratory indicators that the investigator believes will affect the research results or are not in line with the interests of the subject should be excluded.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Liu, M.D.
Phone
+862122200000
Ext
3602
Email
drjunliu@qq.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaolong Fu, M.D.
Phone
+862122200000
Ext
3602
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Liu, M.D.
Organizational Affiliation
Shanghai Chest Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Chest Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Liu, M.D.

12. IPD Sharing Statement

Learn more about this trial

Camrelizumab Combined With Neoadjuvant Concurrent Chemoradiotherapy for Resectable Locally Advanced ESCC(NICE-RT)

We'll reach out to this number within 24 hrs