A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma

Sponsor

National Cancer Center, Japan (Other)

Overall Status

Recruiting

CT.gov ID

NCT03914443

Collaborator

Ono Pharmaceutical Co. Ltd (Industry), Fiverings Co., Ltd. (Other)

Enrollment

Location

Arms

44.9

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Esophageal Squamous Cell Carcinoma	Biological: Nivolumab Drug: 5-FU Drug: CDDP Drug: DTX	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma FRONTiER Trial

Actual Study Start Date :

May 7, 2019

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A "Nivolumab: 360 mg, every 3 week 5-FU: 800 mg/m^2, every 3 week CDDP: 80 mg/m^2, every 3 week "	Biological: Nivolumab 240 mg or 360 mg Other Names: ONO-4538 Drug: 5-FU 750 or 800 mg^2 Other Names: 5-Fluorouracil Drug: CDDP 70 or 80 mg/m^2 Other Names: Cisplatin
Experimental: Cohort B "Nivolumab: 240 mg lead-in followed by 360 mg, every 3 week 5-FU: 800 mg/m^2, every 3 week CDDP: 80 mg/m^2, every 3 week "	Biological: Nivolumab 240 mg or 360 mg Other Names: ONO-4538 Drug: 5-FU 750 or 800 mg^2 Other Names: 5-Fluorouracil Drug: CDDP 70 or 80 mg/m^2 Other Names: Cisplatin
Experimental: Cohort C "Nivolumab: 360 mg, every 3 week 5-FU: 750 mg/m^2, every 3 week CDDP: 70 mg/m^2, every 3 week DTX: 70mg/m^2, every 3 weeks"	Biological: Nivolumab 240 mg or 360 mg Other Names: ONO-4538 Drug: 5-FU 750 or 800 mg^2 Other Names: 5-Fluorouracil Drug: CDDP 70 or 80 mg/m^2 Other Names: Cisplatin Drug: DTX 70 mg/m^2 Other Names: Docetaxel
Experimental: Cohort D "Nivolumab: 240 mg lead-in followed by 360 mg, every 3 week 5-FU: 750 mg/m^2, every 3 week CDDP: 70 mg/m^2, every 3 week DTX: 70mg/m^2, every 3 weeks"	Biological: Nivolumab 240 mg or 360 mg Other Names: ONO-4538 Drug: 5-FU 750 or 800 mg^2 Other Names: 5-Fluorouracil Drug: CDDP 70 or 80 mg/m^2 Other Names: Cisplatin Drug: DTX 70 mg/m^2 Other Names: Docetaxel

Outcome Measures

Primary Outcome Measures

Rate of participants with dose limiting toxicities (DLTs) [from initial dose to 30 post-operative days]
To evaluate the safety of combination chemotherapy with nivolumab as neoadjuvant Tx

Secondary Outcome Measures

Response rate (RR): percentage of participants with with a best response of CR or PR [from baseline to date of disease progression, approximately 24 months]
To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx
Pathological complete response rate [from baseline to operation, average of 10 weeks after initial dose]
To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx
Radical resection rate [at operation, average of 10 weeks after initial dose]
To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx
Treatment completion rate [from baseline to operation, average of 10 weeks after initial dose]
To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx
Adverse event (AE) expression rate [up to 30 postoperative days]
To evaluate the safety of combination chemotherapy with nivolumab as neoadjuvant Tx
Progression-free survival (PFS) [from baseline to date of disease progression or death, approximately 24 month]
To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx
Overall survival (OS) [from baseline to date of death, approximately 24 month]
To evaluate the efficacy of combination chemotherapy with nivolumab as neoadjuvant Tx

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Endoscopic biopsy of esophageal primary lesion histologically diagnosed as squamous cell carcinoma, adenosquamous carcinoma or basal cell carcinoma
All esophageal cancer lesions are localized in the thoracic esophagus
Patients are classified as clinical stage T1N1-3M0 or T2-3N0-3M0 in the UICC-TNM classification 8th edition
The age is over 20 years old and under 75 on the enrollment date
PS 0-1
With or without measurable lesions
Patients who have no medical history of treatment for esophageal cancer
Patients who have no medical history of chemotherapy, radiotherapy and endocrine therapy including treatment for other types of cancer
The results of laboratory tests within 14 days before enrollment meet the inclusion criteria
Esophageal cancer radical surgery (R0) by open-chest surgery (or thoracoscopic surgery) and laparotomy (or laparoscopic surgery) is judged possible
Patients who have no complication or history of thyroid dysfunction
Patients who have no complication or history of autoimmune disease
Patients who don't have treatment with systemic corticostroids (dose of 10mg/day over in prednisolone equivalent) or imunosuppressants within 14 days before enrollment
Patinets who have no complication or hisoty of pneumonitis or pulmonary fibrosis which had been diagnosed by imaging tests or phisical examination
For females, who have agreed with contraception from start of investigational drug administration to 5 months after last dose of investigational drug. For males who have agreed with contraception from start of investigational drug administration to 7 months after last dose of investigational drug.
Obtained the written informed consent from patients"

Exclusion criteria:

Patients who have active multiple cancers
Patients who have infectious disease which is active and need the systemic treatment
Positive with HBs antigen, or HCV-RNA or anti HIV antibody, or anti HTLV-1 antibody tests
Negative with HBs antigen test and positive with anti HBs antibody or anti HBc antibody tests, and positive with HBV-DNA quantitative test
Pregnant, suspected pregnant or lactating
Patients who have Psycosis or psychiatric symptoms are judged inappropriate for paticipation of the trial
Patients who need the treatment with continued use of flucytosine, phenytoin or warfalin pottasium
Ptients who have a medical history of allergy to iodine
Patients who have hypersensitivity to docetaxel, cisplatin, and drug containing polysorbate 80
Patients who have a complication or a history of highly sensitive reactions to antibody formulations
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
Patients who have advanced pulmonary emphysema which is observed by pulmonary function test or CT test
Patients who have uncontrollable hypertension
Patients who have unstable angina or a medical history of myocardial infarction within 6 months before for enrollment
Patients who have diverticulitis or symptomatic peptic ulcer disease
Patients who have history of transplantation therapy such as hematopoietic stem cell transplantation
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"