Clinical trial NCT03914443: A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma
Official title: A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma FRONTiER Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma
Keywords: Esophageal squamous cell carcinoma
Neoadjuvant chemotherapy
Nivolumab
JCOG
Lead sponsor: National Cancer Center, Japan
Sponsor class: OTHER_GOV
Collaborators: name: Ono Pharmaceutical Co. Ltd
name: Fiverings Co., Ltd.
First posted: 2019-04-16
Enrollment: 37
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety of the neoadjuvant therapy, nivolumab with CF (5-FU, CDDP) or nivolumab with DCF (5-FU, CDDP, DTX), for locally advanced esophageal carcinoma.


Eligibility criteria: Inclusion 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 20 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 don't have treatment with systemic corticosteroids (dose of 10mg/day over in prednisolone equivalent) or immunosuppressants within 14 days before enrollment
14. Patients who have no complication or history of pneumonitis or pulmonary fibrosis which had been diagnosed by imaging tests or physical examination
15. For females, who have agreed with contraception from start of investigational drug administration to 5 months after last dose of an investigational drug. For males who have agreed with contraception from start of investigational drug administration to 7 months after last dose of an investigational drug.
16. Obtained written informed consent from patients"

Exclusion criteria:

1. Patients who have active multiple cancers
2. Patients who have an infectious disease that is active and need the systemic treatment
3. Positive with HBs antigen, 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 participation in the trial
7. Patients who need the treatment with continued use of flucytosine, phenytoin, or warfarin potassium
8. Patients who have a medical history of allergy to iodine
9. Patients who have hypersensitivity to docetaxel, cisplatin, 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 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 enrollment
15. Patients who have diverticulitis or symptomatic peptic ulcer disease
16. Patients who have a history of transplantation therapy, such as hematopoietic stem cell transplantation
17. Patients who have a medical history of treatment with an 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."

Primary outcomes:
measure: Rate of participants with dose limiting toxicities (DLTs)
timeFrame: from initial dose to 30 post-operative days
Secondary outcomes:
measure: Response rate (RR): percentage of participants with with a best response of CR or PR
timeFrame: from baseline to date of disease progression, approximately 24 months
measure: Pathological complete response rate
timeFrame: from baseline to operation, average of 10 weeks after initial dose
measure: Radical resection rate
timeFrame: at operation, average of 10 weeks after initial dose
measure: Treatment completion rate
timeFrame: from baseline to operation, average of 10 weeks after initial dose
measure: Adverse event (AE) expression rate
timeFrame: up to 30 postoperative days
measure: Progression-free survival (PFS)
timeFrame: from baseline to date of disease progression or death, approximately 24 month
measure: Overall survival (OS)
timeFrame: from baseline to date of death, approximately 24 month
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
Study officials:
affiliation: Department of Gastrointestinal Medical Oncology, National cancer center hospital
name: Ken Kato, MD/PhD
role: STUDY_CHAIR
References:
citation: Yamamoto S, Kato K, Daiko H, Kojima T, Hara H, Abe T, Tsubosa Y, Nagashima K, Aoki K, Mizoguchi Y, Kitano S, Yachida S, Shiba S, Kitagawa Y. Feasibility study of nivolumab as neoadjuvant chemotherapy for locally esophageal carcinoma: FRONTiER (JCOG1804E). Future Oncol. 2020 Jul;16(19):1351-1357. doi: 10.2217/fon-2020-0189. Epub 2020 May 12.