Clinical trial NCT03731442: Salvage Chemoradiation Therapy for Recurrence After Radical Surgery or Palliative Surgery in Esophageal Cancer Patients
Official title: Salvage Chemoradiation Therapy for Recurrence After Radical Surgery or Palliative Surgery in Esophageal Cancer Patients: A Prospective, Multicenter Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Esophageal Cancer
Keywords: Salvage therapy
Recurrence
Chemoradiation
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
Collaborators: name: The First Affiliated Hospital with Nanjing Medical University
name: Tianjin Medical University Cancer Institute and Hospital
name: Anyang Tumor Hospital
name: Fujian Cancer Hospital
name: Peking University Cancer Hospital & Institute
name: Hebei Medical University Fourth Hospital
First posted: 2018-11-06
Enrollment: 300
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Currently, adjuvant therapy is not recommended for patients with esophageal squamous cell carcinoma who received radical surgery. However, the recurrence rate is as high as 23.8%-58%, and the median time-to-recurrence is about 10.5 months. In patients who had residual tumor after surgery, evidence lacks for chemoradiation. The aim of the study is to evaluate the efficacy and safety of chemoradiation therapy in patients with recurrences after radical surgery or palliative surgery.

Detailed description: Currently, adjuvant therapy is not recommended for patients with esophageal squamous cell carcinoma who received surgery as their first treatment. However, the recurrence rate is as high as 23.8%-58%, and the median time-to-recurrence is about 10.5 months. In patients who had residual tumor after surgery, evidence lacks for chemoradiation.

Retrospective data of 218 cases in our hospital indicated patients underwent salvage chemoradiation had significantly improved survival compared with chemotherapy, radiotherapy or best supportive care. For patients with locoregional recurrence, the 1-, 3-year overall survival (OS) rates were statistically higher in patients received salvage chemoradiation than radiotherapy (1-year OS, 70.0% vs. 55.2%, 3-year OS, 41.9% vs. 23.5%, p=0.045). Patients received chemotherapy had 1-year OS of 0%.

Data of 218 cases of our hospital indicated patients received radiation dose \> 54Gy had a significantly longer median overall survival time of 21.2 months compared with 11.3 months in patients had \<54Gy. The optimal radiation dose should be further investigated.

The recurrence pattern of patients with esophageal cancer after esophagectomy mainly consist of supraclavicular and mediastinal lymph nodes. For patients recurred after radical surgery, prophylactic irradiation to high-risk lymph node regions should be considered. The study use simultaneously integrated boost (SIB) intensity-modulated radiation therapy (IMRT) in this trial, which made different radiation dose to recurrent tumor and high-risk lymph node regions possible.

The aim of the study is to evaluate the efficacy and safety of chemoradiation therapy in patients with recurrences after radical surgery or palliative surgery. Patients were further assigned to receive elective field irradiation (ENI) or involved field irradiation (IFI) according to tumor size, tumor location and time-to-recurrence.

Eligibility criteria: Inclusion Criteria:

* Locoregional recurrence after radical surgery;
* Positive resection margin (R1/R2) after surgery;
* Out-of-field recurrence after adjuvant chemoradiation or radiotherapy;
* Recurrence after adjuvant chemotherapy;
* No prior therapy after recurrence;
* Age 16-70 years;
* KPS\>70;
* No history of drug allergy;
* Sufficient liver and kidney functions;
* White blood cell count \> 4.0\*10\^9/L.

Exclusion Criteria:

* Age\>70 or \<16 years;
* Pregnancy or lactation;
* History of drug allergy;
* Declining informed consent;
* Insufficient liver or kidney functions, or abnormal CBC test;
* Severe cardiovascular diseases, infections, active ulcerations, diabetes mellitus with unstable blood sugar, mental disorders.

Primary outcomes:
measure: 1-, 2-, 3-year overall survival
timeFrame: From treatment initiation to death from any cause or censor, assessed up to 36 months
Secondary outcomes:
measure: 1-, 2-, 3-year local progression-free survival
timeFrame: From treatment initiation to first documented local progression or death or censor, assessed up to 36 months
measure: 1-, 2-, 3-year progression-free survival
timeFrame: From treatment initiation to first documented progression or death or censor, assessed up to 36 months
measure: Simultaneously integrated boost radiation therapy completion rate
timeFrame: During chemoradation, assessed up to 60 days
measure: Toxicities according to RTOG and CTCAE criteria, including hematological and non-hematological toxicities
timeFrame: Assessed within 3 months from initiation of chemoradiaiton (acute), and 3 months after initiation of chemoradiation (late), according to RTOG and CTCAE criteria, including hematological and non-hematological toxicities
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
state: Beijing
Study officials:
References:
citation: Chang X, Deng L, Ni W, Li C, Han W, Gao LR, Wang S, Zhou Z, Chen D, Feng Q, Liang J, Bi N, Lv J, Gao S, Mao Y, Xue Q, Xiao Z. Salvage chemoradiation therapy for recurrence after radical surgery or palliative surgery in esophageal cancer patients: a prospective, multicenter clinical trial protocol. BMC Cancer. 2020 Sep 14;20(1):877. doi: 10.1186/s12885-020-07315-0.