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Chemoradiation Plus Tislelizumab for Conversion Therapy of Locally Nonresectable ESCC (LATE)

Primary Purpose

Esophageal Squamous Cell Carcinoma, Tislelizumab, Chemoradiation

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
Paclitaxel
Carboplatin
Radiotherapy
Sponsored by
Jiangsu Cancer Institute & Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring ESCC, Esophageal Squamous Cell Carcinoma, Tislelizumab, Chemoradiation, Conversion therapy, Safty, Efficacy

Eligibility Criteria

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

Inclusion Criteria:

  1. Histologically confirmed ESCC;
  2. Clinical stage T4 N-/+,or T1-3 N+(IIIb-IVa) (AJCC 8 TNM classiftion);
  3. Locally advanced ESCC that are not resectable for primary site and/or lymph nodes evaluated before treatment;
  4. At least one measurable lesion in accordance with RECIST 1.1;
  5. Have a performance status of 0 or 1 on the ECOG Performance Scale;
  6. Expected survival time is greater than 6 months;
  7. The important organs' functions meet the following requirements: the absolute neutrophil count(ANC) ≥1.5×10^9/L; the platelet count ≥100×10^9/L; hemoglobin ≥90g/L; bilirubin is less than or equal to 1.5 times ULN, ALT and AST less than or equal 2.5 times UILN; creatinine clearance rate (CCr) ≥50mL/min; the thyroid function is normal;
  8. Female subjects of childbearing potential have a negative pregnancy test and must agree to take effective contraceptive measures during the study period and within 3 months after the last dose;
  9. Be willing and able to provide written informed consent/assent for the trial.

Exclusion Criteria:

  1. The patient has received radiotherapy, chemotherapy, hormone therapy, surgery, or molecular-targeted therapy;
  2. Confirmed patients with distant metastasis by CT imaging;
  3. The subject has previous or co-existing other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
  4. The subject had previously received other anti-PD-1 antibody therapy or other immunotherapy targeting PD-1 / PD-L1;
  5. Patients with active autoimmune disease or documented autoimmune disease or symptoms requiring systemic hormone therapy or anti-autoimmune drug therapy;
  6. Patients with immunodeficiency or who were still receiving systemic steroid hormone therapy (prednisone > 10 mg/ day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days prior to the first dose of neoadjuvant therapy in this study;
  7. Clinical ascites or pleural effusion requiring therapeutic puncture or drainage;
  8. The subject with uncontrol cardiac clinical symptoms or diseases, such as (1) any class 2 or more heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant ventricular or ventricular arrhythmias requiring treatment or intervention;
  9. Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg> 2G /L), bleeding tendency, or receiving thrombolytic or anticoagulant treatment;
  10. The subject is present (within 3 months) with esophageal varices, active gastric and duodenal ulcers, ulcerative colitis, portal hypertension, and other gastrointestinal diseases, or with active bleeding from unresected tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by the investigator;
  11. Past or present severe bleeding (bleeding >30 ml within 3 months), hemoptysis (fresh blood >5 ml within 4 weeks) or thromboembolism events (including stroke events and/or TRANSIENT ischemic attack) within 12 months;
  12. Patients with active infection who still required systemic treatment 7 days before the first dose of neoadjuvant therapy in this study;
  13. Patients with past or present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, severely impaired lung function, etc;
  14. Senior or uncontrolled virus injection: HIV, TP, hepatitis virus;
  15. Patients who had participated in clinical trials of other drugs within 4 weeks;
  16. The live vaccine was administered less than 4 weeks prior to study administration or possibly during the study period;
  17. Have a history of mental illness or psychiatric substance abuse;
  18. The subject cannot or does not agree to bear the cost of the self-paid portion of the examination and treatment, except for the clinical study drug, combined chemoradiotherapy, and SAE associated with the clinical study drug;
  19. Other patients whom the medical practitioner considers inappropriate for inclusion.

Sites / Locations

  • Jiangsu Cancer Institute & HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tislelizumab plus chemoradiation group

Arm Description

In the single experimental arm, patients with nonresectable stage IIIb-IVa disease were subjected to receive neoadjuvant tislelizumab (200mg) plus chemoradiation (TP regimen plus 30Gy/12F irradiation) for conversion therapy. If conversion therapy succeeds, patients would proceed to surgery and adjuvant therapy. Otherwise, if patients were still not resectable after the conversion therapy, an additional radiation dose of 15Gy/6F would be scheduled for the ESCC lesions to achieve a definite radiotherapy dose, then, patients proceeded to consolidation therapy.

Outcomes

Primary Outcome Measures

Treatment safety
The incidence and severity of treatment related adverse event according to CTCAE 5.0

Secondary Outcome Measures

Objective response rate (ORR)
Objective response rate by assessment per RECIST.
Conversion esophagectomy rate (CER)
The ratio of patients succeed to receive esophagectomy after conversion therapy to the number of total patients enrolled in this study and received conversion therapy.
Major pathological response (MPR)
Residual viable tumor of less than or equal to 10% in the reseted samples from whom succeed to surgery after the conversion therapy
Progression free survival (PFS)
The length of time during and after the enrollment of patients without get worse.
Overall survival (OS)
The length of time from the date of enrollment to death for any cause.

Full Information

First Posted
May 24, 2022
Last Updated
May 24, 2022
Sponsor
Jiangsu Cancer Institute & Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05394415
Brief Title
Chemoradiation Plus Tislelizumab for Conversion Therapy of Locally Nonresectable ESCC
Acronym
LATE
Official Title
Chemoradiation Plus tisLelizumAb for Conversion Therapy of Locally Nonresectable ESCC
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2022 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Jiangsu Cancer Institute & 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
This is a single institution and single-arm phase I/II study to assess the feasibility and efficacy of tislelizumab plus chemoradiation for conversion therapy of patients with locally nonresectable ESCC.
Detailed Description
The success of PD-1 antibody immunotherapy has brought about tremendous changes in clinical practice for treating patients with ESCC. Many patients with ESCC were not resectable at first presentation because of locally advanced disease in the primary site and/or in lymph nodes. The primary intention of our study was to evaluate the feasibility and efficacy of combining tislelizumab and chemoradiation for conversion therapy for these patients. The enrolled patients in this study should be with pathologically proved ESCC staged IIIb-IVa according to the 8th edition of UICC/AJCC TNM stage classification. This is a single institution and single-arm phase I/II study, the estimated enrollment was 30 participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma, Tislelizumab, Chemoradiation
Keywords
ESCC, Esophageal Squamous Cell Carcinoma, Tislelizumab, Chemoradiation, Conversion therapy, Safty, Efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tislelizumab plus chemoradiation group
Arm Type
Experimental
Arm Description
In the single experimental arm, patients with nonresectable stage IIIb-IVa disease were subjected to receive neoadjuvant tislelizumab (200mg) plus chemoradiation (TP regimen plus 30Gy/12F irradiation) for conversion therapy. If conversion therapy succeeds, patients would proceed to surgery and adjuvant therapy. Otherwise, if patients were still not resectable after the conversion therapy, an additional radiation dose of 15Gy/6F would be scheduled for the ESCC lesions to achieve a definite radiotherapy dose, then, patients proceeded to consolidation therapy.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
The 1st and 2nd doses were administered concurrently with TP regimen chemotherapy, 200 mg each, on D1 and D22 by intravenous infusion. In patients with successful conversion therapy, one dose of 200 mg on D60, was administered sequentially at the time before surgery after radiation therapy, and two doses of immunotherapy, on D150 and 171, were administered 8 weeks after surgery in concurrent with the 3rd and 4th cycles of chemotherapy as adjuvant therapy; in patients with failed conversion, two doses of chemotherapy combined with tislelizumab, on D60 and D81, were administered 2 weeks after the completion of radiation therapy.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
A TP regimen with paclitaxel 135 mg/m^2 + carboplatin AUC=5 was used, on D1 and D22 infused intravenously. Two cycles of adjuvant chemotherapy, on D150, 171, were started 8 weeks after surgery in patients with a successful conversion, and 2 cycles of consolidation chemotherapy, on D60, 81, were started 2 weeks after the end of radiotherapy in patients with unsuccessful conversion therapy.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
A TP regimen with paclitaxel 135 mg/m^2 + carboplatin AUC=5 was used, on D1, 22 infused intravenously. Two cycles of adjuvant chemotherapy, on D150,171, were started 8 weeks after surgery in patients with a successful conversion, and 2 cycles of consolidation chemotherapy, D60,81, were started 2 weeks after the end of radiotherapy in patients with unsuccessful conversion therapy.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
Radiotherapy was scheduled to be given on D1 of the 2nd cycle of chemotherapy. The primary lesions and/or lymph nodes in the operation area would be radiated in 2 stages. A dose of 30Gy/12F would be given in the first stage. When 12 Fractions were given, our MDT team would evaluate the regression of the lesions according to CT and MR results. If surgery is feasible, radiotherapy would be stopped for the primary lesions and lymph nodes in the operation area; if not resectable, the 2nd stage of radiotherapy would be given with a dose of 15Gy/6F, totaling to 45Gy/18F to the ESCC lesions. Radiotherapy for all lymph nodes outside the operation area was with DT of 45Gy/18F. All radiotherapy in this study was scheduled to be 2.5Gy/F, 1F/d, 5F/w. The preoperative radiotherapy target area was outlined by the consensus of the thoracic surgeon and radiotherapist.
Primary Outcome Measure Information:
Title
Treatment safety
Description
The incidence and severity of treatment related adverse event according to CTCAE 5.0
Time Frame
up to 2 years
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Objective response rate by assessment per RECIST.
Time Frame
up to 2 years
Title
Conversion esophagectomy rate (CER)
Description
The ratio of patients succeed to receive esophagectomy after conversion therapy to the number of total patients enrolled in this study and received conversion therapy.
Time Frame
up to 2 years
Title
Major pathological response (MPR)
Description
Residual viable tumor of less than or equal to 10% in the reseted samples from whom succeed to surgery after the conversion therapy
Time Frame
up to 2 years
Title
Progression free survival (PFS)
Description
The length of time during and after the enrollment of patients without get worse.
Time Frame
up to 2 years
Title
Overall survival (OS)
Description
The length of time from the date of enrollment to death for any cause.
Time Frame
up to 2 years

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: Histologically confirmed ESCC; Clinical stage T4 N-/+,or T1-3 N+(IIIb-IVa) (AJCC 8 TNM classiftion); Locally advanced ESCC that are not resectable for primary site and/or lymph nodes evaluated before treatment; At least one measurable lesion in accordance with RECIST 1.1; Have a performance status of 0 or 1 on the ECOG Performance Scale; Expected survival time is greater than 6 months; The important organs' functions meet the following requirements: the absolute neutrophil count(ANC) ≥1.5×10^9/L; the platelet count ≥100×10^9/L; hemoglobin ≥90g/L; bilirubin is less than or equal to 1.5 times ULN, ALT and AST less than or equal 2.5 times UILN; creatinine clearance rate (CCr) ≥50mL/min; the thyroid function is normal; Female subjects of childbearing potential have a negative pregnancy test and must agree to take effective contraceptive measures during the study period and within 3 months after the last dose; Be willing and able to provide written informed consent/assent for the trial. Exclusion Criteria: The patient has received radiotherapy, chemotherapy, hormone therapy, surgery, or molecular-targeted therapy; Confirmed patients with distant metastasis by CT imaging; The subject has previous or co-existing other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix); The subject had previously received other anti-PD-1 antibody therapy or other immunotherapy targeting PD-1 / PD-L1; Patients with active autoimmune disease or documented autoimmune disease or symptoms requiring systemic hormone therapy or anti-autoimmune drug therapy; Patients with immunodeficiency or who were still receiving systemic steroid hormone therapy (prednisone > 10 mg/ day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days prior to the first dose of neoadjuvant therapy in this study; Clinical ascites or pleural effusion requiring therapeutic puncture or drainage; The subject with uncontrol cardiac clinical symptoms or diseases, such as (1) any class 2 or more heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant ventricular or ventricular arrhythmias requiring treatment or intervention; Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg> 2G /L), bleeding tendency, or receiving thrombolytic or anticoagulant treatment; The subject is present (within 3 months) with esophageal varices, active gastric and duodenal ulcers, ulcerative colitis, portal hypertension, and other gastrointestinal diseases, or with active bleeding from unresected tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by the investigator; Past or present severe bleeding (bleeding >30 ml within 3 months), hemoptysis (fresh blood >5 ml within 4 weeks) or thromboembolism events (including stroke events and/or TRANSIENT ischemic attack) within 12 months; Patients with active infection who still required systemic treatment 7 days before the first dose of neoadjuvant therapy in this study; Patients with past or present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, severely impaired lung function, etc; Senior or uncontrolled virus injection: HIV, TP, hepatitis virus; Patients who had participated in clinical trials of other drugs within 4 weeks; The live vaccine was administered less than 4 weeks prior to study administration or possibly during the study period; Have a history of mental illness or psychiatric substance abuse; The subject cannot or does not agree to bear the cost of the self-paid portion of the examination and treatment, except for the clinical study drug, combined chemoradiotherapy, and SAE associated with the clinical study drug; Other patients whom the medical practitioner considers inappropriate for inclusion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiangzhi Zhu, Dr.
Phone
+8618915969102
Email
13182948068@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hongliang Yu, Dr.
Phone
+8618625176270
Email
yhllove1@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiangzhi Zhu, Dr.
Organizational Affiliation
Jiangsu Cancer Institute & Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Jiangsu Cancer Institute & Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210001
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiangzhi Zhu, Dr.
Phone
+8618915969102
Email
13182948068@163.com
First Name & Middle Initial & Last Name & Degree
Hongliang Yu, Dr.
Phone
+8618625176270
Email
yhllove1@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Chemoradiation Plus Tislelizumab for Conversion Therapy of Locally Nonresectable ESCC

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