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

November 8, 2023 updated by: National Cancer Center, Japan

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Tokyo, Japan
        • National Cancer Center Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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."

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of participants with dose limiting toxicities (DLTs)
Time Frame: from initial dose to 30 post-operative days
To evaluate the safety of combination chemotherapy with nivolumab as neoadjuvant Tx
from initial dose to 30 post-operative days

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Center, Japan

Collaborators

Ono Pharmaceutical Co. Ltd
Fiverings Co., Ltd.

Investigators

  • Study Chair: Ken Kato, MD/PhD, Department of Gastrointestinal Medical Oncology, National cancer center hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 7, 2019

Primary Completion (Actual)

February 1, 2023

Study Completion (Estimated)

March 1, 2024

Study Registration Dates

First Submitted

April 11, 2019

First Submitted That Met QC Criteria

April 12, 2019

First Posted (Actual)

April 16, 2019

Study Record Updates

Last Update Posted (Estimated)

November 9, 2023

Last Update Submitted That Met QC Criteria

November 8, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JCOG1804E

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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