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

National Cancer Center, Japan

Status and phase: Completed; Phase 1

Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma

Treatments: Biological: Nivolumab; Drug: 5-FU; Drug: CDDP; Drug: DTX

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03914443

JCOG1804E

Details and patient eligibility

About

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.

Enrollment: 37 patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

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."

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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37 participants in 4 patient groups

Cohort A

Experimental group

Description:

"Nivolumab: 360 mg, every 3 week 5-FU: 800 mg/m\^2, every 3 week CDDP: 80 mg/m\^2, every 3 week "

Treatment:

Drug: CDDP

Drug: 5-FU

Biological: Nivolumab

Cohort B

Experimental group

Description:

"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 "

Treatment:

Drug: CDDP

Drug: 5-FU

Biological: Nivolumab

Cohort C

Experimental group

Description:

"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"

Treatment:

Drug: DTX

Drug: CDDP

Drug: 5-FU

Biological: Nivolumab

Cohort D

Experimental group

Description:

"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"

Treatment:

Drug: DTX

Drug: CDDP

Drug: 5-FU

Biological: Nivolumab