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

Locally Advanced Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03914443
• Other study ID #: JCOG1804E
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 7, 2019
• Est. completion date: March 1, 2024

Study information

• Verified date: November 2023
• Source: National Cancer Center, Japan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: March 1, 2024
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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."

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma
• Locally Advanced Esophageal Squamous Cell Carcinoma

Intervention

Biological:
• Nivolumab
240 mg or 360 mg

Drug:
• 5-FU
750 or 800 mg^2
• CDDP
70 or 80 mg/m^2
• DTX
70 mg/m^2

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Tokyo

Sponsors (3)

Lead Sponsor	Collaborator
National Cancer Center, Japan	Fiverings Co., Ltd., Ono Pharmaceutical Co. Ltd

Country where clinical trial is conducted

Japan, 

Outcome

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