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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03914443
Recruitment Status : Active, not recruiting
First Posted : April 16, 2019
Last Update Posted : September 10, 2020
Sponsor:
Collaborators:
Ono Pharmaceutical Co. Ltd
Fiverings Co., Ltd.
Information provided by (Responsible Party):
National Cancer Center, Japan

Tracking Information
First Submitted Date  ICMJE April 11, 2019
First Posted Date  ICMJE April 16, 2019
Last Update Posted Date September 10, 2020
Actual Study Start Date  ICMJE May 7, 2019
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • 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
  • 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
  • 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
  • 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
  • Adverse event (AE) expression rate [ Time Frame: up to 30 postoperative days ]
    To evaluate the safety of combination chemotherapy with nivolumab as neoadjuvant Tx
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma
Official Title  ICMJE A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma FRONTiER Trial
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Locally Advanced Esophageal Squamous Cell Carcinoma
Intervention  ICMJE
  • Biological: Nivolumab
    240 mg or 360 mg
    Other Name: ONO-4538
  • Drug: 5-FU
    750 or 800 mg^2
    Other Name: 5-Fluorouracil
  • Drug: CDDP
    70 or 80 mg/m^2
    Other Name: Cisplatin
  • Drug: DTX
    70 mg/m^2
    Other Name: Docetaxel
Study Arms  ICMJE
  • 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 "
    Interventions:
    • Biological: Nivolumab
    • Drug: 5-FU
    • Drug: CDDP
  • 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 "
    Interventions:
    • Biological: Nivolumab
    • Drug: 5-FU
    • Drug: CDDP
  • 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"
    Interventions:
    • Biological: Nivolumab
    • Drug: 5-FU
    • Drug: CDDP
    • Drug: DTX
  • 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"
    Interventions:
    • Biological: Nivolumab
    • Drug: 5-FU
    • Drug: CDDP
    • Drug: DTX
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 12, 2019)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 1, 2022
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 corticostroids (dose of 10mg/day over in prednisolone equivalent) or imunosuppressants within 14 days before enrollment
  14. Patinets who have no complication or hisoty of pneumonitis or pulmonary fibrosis which had been diagnosed by imaging tests or phisical examination
  15. 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.
  16. Obtained the written informed consent from patients"

Exclusion criteria:

  1. Patients who have active multiple cancers
  2. Patients who have infectious disease which is active and need the systemic treatment
  3. Positive with HBs antigen, or 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 paticipation of the trial
  7. Patients who need the treatment with continued use of flucytosine, phenytoin or warfalin pottasium
  8. Ptients 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 to 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 for enrollment
  15. Patients who have diverticulitis or symptomatic peptic ulcer disease
  16. Patients who have history of transplantation therapy such as hematopoietic stem cell transplantation
  17. 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"
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03914443
Other Study ID Numbers  ICMJE JCOG1804E
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party National Cancer Center, Japan
Study Sponsor  ICMJE National Cancer Center, Japan
Collaborators  ICMJE
  • Ono Pharmaceutical Co. Ltd
  • Fiverings Co., Ltd.
Investigators  ICMJE
Study Chair: Ken Kato, MD/PhD Department of Gastrointestinal Medical Oncology, National cancer center hospital
PRS Account National Cancer Center, Japan
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP