Chemoradiation Plus Tislelizumab for Conversion Therapy of Locally Nonresectable ESCC

NCT05394415 | Unknown Phase 1

• 1 other identifier: 2022-020-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Squamous Cell Carcinoma; Tislelizumab; Chemoradiation

Keywords

ESCC; Esophageal Squamous Cell Carcinoma; Tislelizumab; Chemoradiation; Conversion therapy; Safty; Efficacy

Outcome Measures

Primary Outcomes (1)

• Treatment safety

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

  up to 2 years

Secondary Outcomes (5)

• Objective response rate (ORR)

  up to 2 years

• Conversion esophagectomy rate (CER)

  up to 2 years

• Major pathological response (MPR)

  up to 2 years

• Progression free survival (PFS)

  up to 2 years

• Overall survival (OS)

  up to 2 years

Study Arms (1)

Tislelizumab plus chemoradiation group

EXPERIMENTAL

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.

Drug: Tislelizumab; Drug: Paclitaxel; Drug: Carboplatin; Radiation: Radiotherapy

Interventions

Tislelizumab DRUG

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.

Tislelizumab plus chemoradiation group

Paclitaxel DRUG

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.

Tislelizumab plus chemoradiation group

Carboplatin DRUG

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.

Tislelizumab plus chemoradiation group

Radiotherapy RADIATION

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.

Tislelizumab plus chemoradiation group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Jiangsu Cancer Institute & Hospital: lead

Study Sites (1)

Jiangsu Cancer Institute & Hospital

Nanjing, Jiangsu, 210001, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

tislelizumab; Paclitaxel; Carboplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Therapeutics

Study Officials

• Xiangzhi Zhu, Dr.

  Jiangsu Cancer Institute & Hospital

  STUDY DIRECTOR

Central Study Contacts

Xiangzhi Zhu, Dr.

CONTACT

+8618915969102; 13182948068@163.com

Hongliang Yu, Dr.

CONTACT

+8618625176270; yhllove1@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: May 24, 2022
• First Posted: May 27, 2022
• Study Start: May 1, 2022
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2025
• Last Updated: May 27, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)