Adding PD-1 inhibitors to neoadjuvant chemoradiotherapy has shown promising results in locally advanced resectable esophageal squamous cell carcinoma (ESCC). However, there is a need to explore safer and more effective treatment doses and schedules. This is an open labeled, prospective, single-arm phase II trial to evaluate the safety and efficacy of the short course neoadjuvant chemo-radiotherapy plus Toripalimab for locally advanced resectble ESCC.
Although neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced ESCC, prognosis of these patients is still poor. Adding PD-1/PD-L1 checkpoints inhibitor to neoadjuvant chemoradiotherapy (CRT) have shown potential benefit in locally advanced resectble ESCC. However, the conventional radiation dose may lead to irreversible toxicity. There is need to explore more effective and safer treatment doses and schedules for this combination. The investigators proposed a novel strategy (short course neoadjuvant radiotherapy plus preoperative chemotherapy and toripalimab, the SCALE strategy) for the treatment of locally advanced resectble ESCC. In the phase Ib SCALE-1 (ChCTR2100045104) study, 23 patients were enrolled and 20 patients had undergone surgery after the preoperative treatment. The preliminary results showed that the SCALE strategy was safe and induced a pCR and MPR in 55% and 80% of resected tumors, respectively. In this prospective, phase II study, the investigators will further evaluate the safety and efficacy of the SCALE strategy in locally advanced resectble ESCC. This study will provide valuable information for further clinical use of SCALE strategy in locally advanced resectble ESCC.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Paclitaxel (135 mg /m2) and carboplatin (AUC=5) every 3 weeks for two cycles (D1,D22)
Toripalimab 240mg every 3 weeks for two cycles (D2,D23)
30 Gy in 12 fractions, 1 fraction per day, 5 days per week, D3-D18
Jiangsu Cancer Hospital /Jiangsu Institute of Cancer Research
Nanjing, Jiangsu, China
RECRUITINGPathologic complete response
Pathologic complete response was defined as pT0N0M0 or pTisN0M0
Time frame: 1 month after resection
Disease free survival
Disease free survival defined as the time from enrollment to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.
Time frame: 3 years after resection
3-year overall survival
Defined as from date of enrollment until the date of death from any cause or the date of last follow-up, whichever came first.
Time frame: 3 years after enrollment
Incidence of Treatment-related Adverse Events
The neoadjuvant treatment-related adverse events as assessed by CTCAE v5.0
Time frame: From the date of enrollment until surgery was applied during study period or up to at least 90 days after last dose
Perioperative complication rate
The perioperative complication rate of esophagectomy using clavien-Dindo classification
Time frame: From date of surgery to 30 days later
Health related quality of Life
To compare change in Quality of Life, as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 (Version 3)) during the neoadjuvant therapy and perioperative period. The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. The EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). Half points are not allowed. The range is 6. First of all, raw score has to be calculated with mean values. Afterwards linear transformation is performed to be comparable. More points are considered to have a better outcome.
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Time frame: Measured before and after neoadjuvant therapy, before and 1, 3, 6, 9, 12 months after surgery.
Health related quality of Life related to esophageal carcinoma
To compare change in Quality of Life in esophageal carcinoma patients, the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire for Esophageal Cancer (EORTC QLQ-QES18) was used. The EORTC QLQ-QES18 uses for the questions 1 to 18 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome.
Time frame: Measured before and after neoadjuvant therapy, before and 1, 3, 6, 9, 12 months after surgery.