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

NCT03914443 | Completed Phase 1 DMC

• 1 other identifier: JCOG1804E
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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

Keywords

Esophageal squamous cell carcinoma; Neoadjuvant chemotherapy; Nivolumab; JCOG

Outcome Measures

Primary Outcomes (1)

• Rate of participants with dose limiting toxicities (DLTs)

  To evaluate the safety of combination chemotherapy with nivolumab as neoadjuvant Tx

  from initial dose to 30 post-operative days

Secondary Outcomes (7)

• 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

• Pathological complete response rate

  from baseline to operation, average of 10 weeks after initial dose

• Radical resection rate

  at operation, average of 10 weeks after initial dose

• Treatment completion rate

  from baseline to operation, average of 10 weeks after initial dose

• Adverse event (AE) expression rate

  up to 30 postoperative days

Study Arms (4)

Cohort A

EXPERIMENTAL

"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; Drug: 5-FU; Drug: CDDP

Cohort B

EXPERIMENTAL

"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; Drug: 5-FU; Drug: CDDP

Cohort C

EXPERIMENTAL

"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; Drug: 5-FU; Drug: CDDP; Drug: DTX

Cohort D

EXPERIMENTAL

"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; Drug: 5-FU; Drug: CDDP; Drug: DTX

Interventions

Nivolumab BIOLOGICAL

240 mg or 360 mg

Also known as: ONO-4538

Cohort A; Cohort B; Cohort C; Cohort D

5-FU DRUG

750 or 800 mg\^2

Also known as: 5-Fluorouracil

Cohort A; Cohort B; Cohort C; Cohort D

CDDP DRUG

70 or 80 mg/m\^2

Also known as: Cisplatin

Cohort A; Cohort B; Cohort C; Cohort D

DTX DRUG

70 mg/m\^2

Also known as: Docetaxel

Cohort C; Cohort D

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 corticosteroids (dose of 10mg/day over in prednisolone equivalent) or immunosuppressants within 14 days before enrollment
• Patients who have no complication or history of pneumonitis or pulmonary fibrosis which had been diagnosed by imaging tests or physical examination
• 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.
• Obtained written informed consent from patients"

You may not qualify if:

• Patients who have active multiple cancers
• Patients who have an infectious disease that is active and need the systemic treatment
• Positive with HBs antigen, 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 participation in the trial
• Patients who need the treatment with continued use of flucytosine, phenytoin, or warfarin potassium
• Patients 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 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 enrollment
• Patients who have diverticulitis or symptomatic peptic ulcer disease

Sponsors & Collaborators

• National Cancer Center, Japan: lead
• Ono Pharmaceutical Co. Ltd: collaborator
• Fiverings Co., Ltd.: collaborator

Study Sites (1)

National Cancer Center Hospital

Tokyo, Japan

Location

Related Publications (1)

• 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.

  PMID: 32396014 DERIVED

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Nivolumab; Fluorouracil; Cisplatin; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Ken Kato, MD/PhD

  Department of Gastrointestinal Medical Oncology, National cancer center hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2019
• First Posted: April 16, 2019
• Study Start: May 7, 2019
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: May 31, 2025

Record last verified: 2025-05

Locations

JP (1)