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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
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.
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.
Jiangsu Cancer Institute & Hospital
Nanjing, Jiangsu, China
RECRUITINGTreatment safety
The incidence and severity of treatment related adverse event according to CTCAE 5.0
Time frame: up to 2 years
Objective response rate (ORR)
Objective response rate by assessment per RECIST.
Time frame: up to 2 years
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.
Time frame: up to 2 years
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
Time frame: up to 2 years
Progression free survival (PFS)
The length of time during and after the enrollment of patients without get worse.
Time frame: up to 2 years
Overall survival (OS)
The length of time from the date of enrollment to death for any cause.
Time frame: up to 2 years
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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.
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.