A feasibility trial of nivolumab with neoadjuvant CF or DCF, FLOT therapy for locally advanced esophageal carcinoma

JRCT ID: jRCT2031180172

Registered date:01/03/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Thoracic esophageal cancer
• Date of first enrollment: 24/05/2019
• Target sample size: 36
• Study type: Interventional
• Intervention(s): CF therapy (5-FU + cisplatin) , DCF therapy (docetaxel + 5-FU + cisplatin) or FLOT (5-FU + levofolinate + oxaliplatin + docetaxel) in combination with nivolumab as neoadjuvant therapy

Outcome(s)

• Primary Outcome: Dose limited toxicity (DLT) expression rate in during neoadjuvant therapy/ during surgery/ from the end of surgery to 30 days after surgery
• Secondary Outcome: Response rate in neoadjuvant therapy, pathologically complete response rate, radical resection rate, treatment completion ratio, adverse event (AE) expression rate (during neoadjuvant therapy, during surgery, early postoperative period or 31 days on and after surgery), progression free survival, overall survival

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

1) Endoscopic biopsy of esophageal primary lesion histologically diagnosed as squamous cell carcinoma, adenosquamous carcinoma or basal cell carcinoma
2) All esophageal cancer lesions are localized in the thoracic esophagus
3) Patients are classified as clinical stage T1N1-3M0 or T2-3N0-3M0 in the UICC-TNM classification 8th edition
4) The age is over 18 years old and under 75 on the enrollment date
5) PS 0-1
6) With or without measurable lesions
7) Patients who have no medical history of treatment for esophageal cancer
8) Patients who have no medical history of chemotherapy, radiotherapy and endocrine therapy including treatment for other types of cancer
9) The results of laboratory tests within 14 days before enrollment meet the inclusion criteria
10) Esophageal cancer radical surgery (R0) by open-chest surgery (or thoracoscopic surgery) and laparotomy (or laparoscopic surgery) is judged possible
11) Patients who have no complication or history of thyroid dysfunction
12) Patients who have no complication or history of autoimmune disease
13) Patients who have no complication or history of active tuberculosis
14) Patients who don't have treatment with systemic corticostroids (dose of 10mg/day over in prednisolone equivalent) or imunosuppressants within 14 days before enrollment
15) Patinets who have no complication or hisoty of pneumonitis or pulmonary fibrosis which had been diagnosed by imaging tests or phisical examination
16) Females who have agreed with contraception and not to donate oocytes from their consent participation of the study, until 5 months after the last dose of nivolumab, 14 months after the last dose of cisplatin, or 9 months after the last dose of oxaliplatin, whichever is later. Males who have agreed with contraception and not to donate sperms from start of cisplatin or oxaliplatin administration, until 11 months after the last dose of cisplatin, or 6 months after the last dose of oxaliplatin, whichever is later
17) Obtained the written informed consent from patients

Exclude criteria

1) Patients who have active multiple cancers
2) Patients who have infectious disease which is active and need the systemic treatment
3) Positive with HBs antigen, or HCV-RNA or anti HIV antibody, or anti HTLV-1 antibody tests
4) Negative with HBs antigen test and positive with anti HBs antibody or anti HBc antibody tests, and positive with HBV-DNA quantitative test
5) Pregnant, suspected pregnant or lactating
6) Patients who have Psycosis or psychiatric symptoms are judged inappropriate for paticipation of the trial
7) Patients who need the treatment with continued use of flucytosine, phenytoin or warfalin pottasium
8) Patients who have a medical history of allergy to iodine
9) Patients who have hypersensitivity to docetaxel, cisplatin, oxaliplatin, and drug containing polysorbate 80
10) Patients who have a complication or a history of highly sensitive reactions to antibody formulations
11) Even if insulin or oral hypoglycemic agent is continued to use, the result of HbA1c test is 6.5% or more in JDS or 6.9% or more in NGSP
12) Patients who have advanced pulmonary emphysema which is observed by pulmonary function test or CT test
13) Patients who have uncontrollable hypertension
14) Patients who have unstable angina or a medical history of myocardial infarction within 6 months before for enrollment
15) Patients who have diverticulitis or symptomatic peptic ulcer disease
16) Patients who have history of transplantation therapy such as hematopoietic stem cell transplantation
17) Patients who have medical history of treatment with anti PD-1 antibody, anti PD-L1 antibody, anti PD-L2 antibody, anti CD137 antibody, anti CTLA-4 antibody or any other antibody for inhibition or modulation of T cell costimulatory pathway or cancer vaccine
18) The patient received or is scheduled to receive live or attenuated vaccine within 28 days prior to the first dose of nivolumab

Related Information

• Primary Sponsor: Kato Ken
• Secondary Sponsor: Kitagawa Yuko
• Source(s) of Monetary Support: ONO PHARMACEUTICAL CO., LTD.