Study of Neoadjuvant Nivolumab or Placebo Plus Chemotherapy Followed by Surgery and Adjuvant Treatment in Subjects With Resectable ESCC

• Status: Not yet recruiting
• Trial end date: 2024-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Esophageal cancer, the 7th most common cancer globally, accounts for more than half a million deaths each year. The incidence of ESCC, the most common histologic type, has been stable, whereas the incidences of esophageal and gastroesophageal junction adenocarcinomas continue to increase in Western countries.

Neoadjuvant chemoradiotherapy followed by surgery has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer, especially in western countries. In Asia, nCT is considered as the standard of care for Stage II/III ESCC based on JCOG9204 and JCOG9907 trials. The superiority of nCRT/nCT, in terms of long-term survival, remains to be elucidated. For Stage II/III ESCC patients with multiple stations of lymph nodes involvement, nCT might be more appropriate for the inaccessibility of radiotherapy.

There are only limited studies on preoperative immune checkpoint inhibitor in combination with chemotherapy followed by surgery for the locally advanced ESCC. Therefore, this study intends to use Nivolumab 360 mg Q3W combined with standard chemotherapy as the neoadjuvant therapy regimen.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Zhongshan Hospital
• Collaborator: Bristol-Myers Squibb
• Treatments: Fluorouracil; Nivolumab; Paclitaxel

Criteria

Inclusion Criteria:

• Patients enrolled in the study must meet all of the following conditions:

1. The patient volunteers to participate in the study, signs a consent form, has good compliance, and obeys the follow-up, and is willing and able to follow the protocol during the study.

2. Male or female, aged ≥18 years and ≤75 years.

3. The ECOG PS score is 0-1.

4. Histologically-confirmed squamous cell carcinoma of the esophagus. Tumors of the esophagus are located in the thoracic cavity.

5. Pre-treatment stage as Stage II-III (cT2N0-1M0, cT3N0-1M0, cT1-3N2M0, AJCC/UICC 8th Edition);

6. Expected lifetime > 1 year.

7. Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction > 50 %.

8. Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests.

9. Adequate bone marrow function (White Blood Cells >4x10^9 /L; Neutrophil >2.0×10^9 /L; Hemoglobin > 90 g/L; platelets>100x10^9 /L). AST, ALT ≤ 3 x ULN (If liver metastases exist, AST and ALT allow ≤ 5 x ULN).

10. Adequate liver function (Total bilirubin <1.5x Upper Level of Normal (ULN); Aspartate transaminase (AST) and Alanine transaminase (ALT) <1.5x ULN).

11. Adequate renal function (Glomerular filtration rate (CCr) >60 ml/min; serum creatinine (SCr) ≤120 μmol/L).

12. All acute toxic effects of previous anti-cancer treatment or surgery were all relieved by NCI-CTCAE version 5.0 ≤ 1 (except for hair loss or other toxic effects that the investigator judges to have no risk to the patient's safety).

13. Have the ability to act autonomously, have the ability to swallow pills, and have no gastrointestinal diseases that affect oral drug absorption.

14. Agree to provide hematology and histology samples.

Exclusion Criteria:

• Patients who meet any of the following conditions will be excluded:

Patients have previously received an anti-PD-1, PD-L1 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

Related to cancer:

1. Patients with non-squamous cell carcinoma histology.

2. Patients with advanced inoperable or metastatic esophageal cancer (M1).

3. Patients without qualified Pre-treatment stage.

4. Patients with another previous or current malignant disease.

Others:

1. Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder.

2. Patients who have autoimmune diseases.

3. Pregnant or lactating women and fertile women who will not be using contraception during the trial.

4. Allergy to any drugs.

5. Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy.

6. Patients who recently or currently taking hormones or immunosuppressive agents.

7. Immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) active infection or known HIV seropositivity; including HBV or HCV surface antigen positive (RNA).