JCOG1510: A phase III study of tri-modality combination therapy with induction docetaxel plus cisplatin and 5-fluorouracil (DCF) vs definitive chemoradiotherapy for locally advanced unresectable squamous cell carcinoma of the thoracic esophagus

JRCT ID: jRCTs031180181

Registered date:05/03/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: locally advanced unresectable squamous cell carcinoma of the thoracic esophagus
• Date of first enrollment: 19/03/2018
• Target sample size: 230
• Study type: Interventional

Intervention(s)

[A]: two courses of chemotherapy with cisplatin (70 mg/m2, 2-h intravenous infusion on day 1) and 5-FU (700 mg/m2, 24-h continuous intravenous infusion on days 1-4) repeated every 4 weeks in combination with radiotherapy (a total dose of 60 Gy in a fraction of 2 Gy five times weekly) followed by two courses of additional chemotherapy with cisplatin (80 mg/m2, 2-h intravenous infusion on day 1), and 5-FU (800 mg/m2, 24-h continuous intravenous infusion on days 1-5) repeated every 4 weeks. Salvage treatment can be performed in accordance with the assessment after chemoradiotherapy.
[B]: three courses of induction chemotherapy with docetaxel (70 mg/m2, 1-h intravenous infusion on day 1), cisplatin (70 mg/m2, 2-h intravenous infusion on day 1), and 5-FU (750 mg/m2, 24-h continuous intravenous infusion on days 1-5) repeated every 3 weeks, followed by conversion surgery or two courses of chemotherapy with cisplatin (70 mg/m2, 2-h intravenous infusion on day 1) and 5-FU (700 mg/m2, 24-h continuous intravenous infusion on days 1-4) repeated every 4 weeks in combination with radiotherapy (a total dose of 60 Gy in a fraction of 2 Gy five times weekly) based on the clinical evaluation. Salvage treatment can be performed in accordance with the assessment after chemoradiotherapy.

Outcome(s)

• Primary Outcome: overall survival
• Secondary Outcome: Progression free survival, Complete response proportion of chemoradiotherapy, Response proportion of DCF (in case of Arm B), Adverse events of DCF and chemoradiotherapy, Late onset adverse events, Perioperative complications

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

1) Histologically proven squamous cell carcinoma, adenosquamous carcinoma or basaloid cell carcinoma by endoscopic biopsy for the primary esophageal tumor.
2) Primary tumor located in thoracic esophagus (the UICC-TNM 7th edition). Tumor invading cervical or abdominal esophagus with indication of definitive radiation therapy and accessory lesions with indication of EMR are eligible.
3) Unresectable esophageal cancer based on cervical to abdominal contrast enhanced CT to fulfill either following A) or B), and patients with both bleeding and symptom related to airway constriction which are induced by esophageal hiatus, esophagorespiratory fistula, esophagomediastinal fistula, or artery invasion are ineligible.
A) cT4b or cT3 that may invade adjacent organs in accordance with UICC-TNM 7th edition and Japanese Classification of Esophageal Cancer 11th edition.
B) Other adjacent organs except esophagus are or may be invaded by regional lymph nodes or supraclavicular lymph nodes metastases, and patients with both unresectabel supraclavicular lymph nodes and celiac artery lymph nodes metastases.
4) No distant metastases except supraclavicular lymph nodes metastases in accordance with cervical to abdominal contrast enhanced CT.
5) Diagnosed by radio oncologists before register as a candidate of definitive radiotherapy in 60 Gy within the dose constraints of other organs. CT for treatment planning before register is not mandatory.
6) Aged 20 to 75 years old.
7) ECOG Performance status 0 or 1.
8) Measurable lesions not required.
9) No prior treatment for esophageal cancer except endoscopic resection.
10) No prior chemotherapy and radiotherapy for any cancer.
11) Sufficient organ functions
12) Agreement with surgical procedure as protocol treatment if R0 esophagectomy is judged as possible.
13) Written informed consent.

Exclude criteria

1) Synchronous or metachronous (within 5 years) malignancies.
2) Prior surgery for head and neck superficial carcinoma within 5 years.
3) Diagnosed with active infectious disease requiring systemic treatment by imaging or bacteriological inspections, and body temperature >= 38 degrees Celsius.
4) Positive for HBs antigen or HIV antibody.
5) Pregnancy, possible pregnancy, within 28 days after delivery or breast-feeding. Male subjects who want pregnancy of their partner.
6) Psychological disorder difficult to participate in this clinical study.
7) Receiving continuous systemic corticosteroid or immunosuppressant treatment.
8) Under treatment by flucytosine, phenytoin, or warfarin potassium.
9) Previous history of allergy to iodine.
10) Diabetes mellitus uncontrollable with continuous use of insulin or hypoglycemic agents.
11) Severe emphysema or pulmonary fibrosis based on chest CT.
12) Uncontrolled arterial hypertension.
13) History of unstable angina pectoris with new onset or exacerbation within three weeks or myocardial infarction within six months before registration.
14) Uncontrolled valvular disease, dilated cardiomyopathy, and hypertrophic cardiomyopathy.

Related Information

• Primary Sponsor: DAIKO Hiroyuki
• Source(s) of Monetary Support: National Cancer Center Japan,Japan Agency for Medical Research and Development
• Secondary ID(s): UMIN000031165