SHR-1210 in Combination With Apatinib and Chemotherapy in Patients With Advanced Esophageal Squamous Cell Cancer

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

SHR-1210, a Novel Anti-PD-1 Antibody, in Combination With Apatinib and Irinotecan/Paclitaxel Liposome Plus Nedaplatin in Patients With Previously Untreated Advanced or Metastatic Esophageal Squamous Cell Cancer: a Phase II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03603756
• Other study ID #: NCC201807010
• Status: Recruiting
• Phase: Phase 2
• Start date: July 31, 2018
• Est. completion date: March 28, 2021

Study information

• Verified date: February 2020
• Source: Chinese Academy of Medical Sciences
• Contact: Jing Huang, MD
• Phone: 86-10-87788102
• Email: huangjingwg[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with previously untreated advanced or metastatic esophageal squamous cell carcinoma are recruited to this prospective non-randomized study comprising two separate cohorts. Patients will receive SHR-1210, a novel anti-PD-1 antibody, with apatinib and either irinotecan or paclitaxel liposome plus nedaplatin. The primary endpoint is to determine the objective response rate (ORR) of patients in both cohorts. The regimen(s) of promising efficacy will be further verified in subsequent randomized studies to define the optimal combination of immunotherapy, anti-angiogenesis and chemotherapy in advanced esophageal cancer patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: March 28, 2021
• Est. primary completion date: March 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Histologically or cytologically confirmed squamous cell carcinoma of the esophagus, locally advanced, unresectable, recurrent or metastatic disease.

2. Have not received prior systemic therapy.

3. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

4. Eastern Collaborative Oncology Group (ECOG) Performance Status = 1.

5. Life expectancy >12 weeks.

6. Adequate organ function.

7. For females of child bearing potential, a negative urine or serum pregnancy test result within 72h before study treatment. Participants of reproductive potential must be willing to use adequate contraception for the course of the study until 2 months after the last dose of any of the drugs in the study.

8. Willing and able to provide written informed consent and comply with the requirements of the study.

Exclusion Criteria:

1. Any previous malignancy, except for non squamous-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix within 5 years prior to study entry.

2. Known central nervous system (CNS) metastases.

3. Prior therapy with any of the immune check-point inhibitors.

4. Known immediate or delayed hypersensitivity reaction to SHR-1210, apatinib, irinotecan, paclitaxel liposome, nedaplatin or their excipients.

5. Subjects with any active autoimmune disease or history of autoimmune disease.

6. Known Human Immunodeficiency Virus (HIV) infection, active Hepatitis B or Hepatitis C infection.

7. Concurrent medical condition requiring the use of cortisol (>10mg/day prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids no more than 10 mg/day prednisone or equivalent.

8. Received a live vaccine within 4 weeks of the first dose of study medication.

9. Hypertension with a blood pressure of systolic> 140 millimeter of mercury (mm Hg) and/or diastolic > 90 mm Hg that is not effectively controlled by anti-hypertensive therapy.

10. Uncontrolled clinically significant heart disease, including but not limited to the following: (1) > NYHA II congestive heart failure; (2) unstable angina, (3) myocardial infarction within the past 1 year; (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention.

11. Unable to swallow oral medications or with gastrointestinal disorders that might interfere with proper absorption of oral drugs.

12. Active digestive ulcer disease, inflammatory bowel disease, intestinal obstruction or any other condition that, in the clinical judgment of the Principal Investigator, may cause severe gastrointestinal bleeding or perforation.

13. Active infection or an unexplained fever > 38.5°C before 4 weeks of enrollment.

14. Unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic conditions.

15. Pregnant or lactating female.

16. Familial, sociological or geographical conditions that, in the clinical judgment of the Principal Investigator, do not permit compliance with the protocol.

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Neoplasms, Squamous Cell

Intervention

Drug:
• SHR-1210
a novel anti-PD-1 antibody
• Apatinib
a VEGFR-2 tyrosine kinase inhibitor
• Irinotecan Injection
cytotoxic agent that binds to topoisomerase I
• Paclitaxel liposome
cytotoxic agent that prevent depolymerization of cellular microtubules
• Nedaplatin
cytotoxic agent that cross-links and denatures strands of DNA

Locations

Country	Name	City	State
China	Jing Huang	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	objective response rate	objective response rate of the patients in cohort 1 and cohort 2	24 months
Secondary	progression-free survival (PFS)	progression-free survival (PFS) of the patients in cohort 1 and cohort 2	24 months
Secondary	overall survival	overall survival of the patients in cohort 1 and cohort 2	24 months
Secondary	treatment-related adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	24 months