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

NCT ID: NCT03914443

Last Updated: 2025-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-07
• Study Completion Date: 2025-03-31

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.

Conditions

Locally Advanced Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 "

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

240 mg or 360 mg

5-FU

Intervention Type: DRUG

750 or 800 mg\^2

CDDP

Intervention Type: DRUG

70 or 80 mg/m\^2

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 "

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

240 mg or 360 mg

5-FU

Intervention Type: DRUG

750 or 800 mg\^2

CDDP

Intervention Type: DRUG

70 or 80 mg/m\^2

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"

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

240 mg or 360 mg

5-FU

Intervention Type: DRUG

750 or 800 mg\^2

CDDP

Intervention Type: DRUG

70 or 80 mg/m\^2

DTX

Intervention Type: DRUG

70 mg/m\^2

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"

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

240 mg or 360 mg

5-FU

Intervention Type: DRUG

750 or 800 mg\^2

CDDP

Intervention Type: DRUG

70 or 80 mg/m\^2

DTX

Intervention Type: DRUG

70 mg/m\^2

Interventions

Nivolumab

240 mg or 360 mg

Intervention Type: BIOLOGICAL

5-FU

750 or 800 mg\^2

Intervention Type: DRUG

CDDP

70 or 80 mg/m\^2

Intervention Type: DRUG

DTX

70 mg/m\^2

Intervention Type: DRUG

Other Intervention Names

ONO-4538; 5-Fluorouracil; Cisplatin; Docetaxel

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

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."

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role: collaborator

Fiverings Co., Ltd.

OTHER

Sponsor Role: collaborator

National Cancer Center, Japan

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ken Kato, MD/PhD

Role: STUDY_CHAIR

Department of Gastrointestinal Medical Oncology, National cancer center hospital

Locations

National Cancer Center Hospital

Tokyo, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 32396014 (View on PubMed)

Other Identifiers

JCOG1804E

Identifier Type: -

Identifier Source: org_study_id