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

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

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.

Study Overview

• Status: Unknown
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: SHR-1210; Drug: Apatinib; Drug: Irinotecan Injection; Drug: Paclitaxel liposome; Drug: Nedaplatin

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianping Xu, MD

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Jing Huang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; Patients with advanced or metastatic esophageal squamous cell carcinoma are to receive SHR-1210 with apatinib and irinotecan injection in cohort 1.	Drug: SHR-1210; a novel anti-PD-1 antibody; Drug: Apatinib; a VEGFR-2 tyrosine kinase inhibitor; Drug: Irinotecan Injection; cytotoxic agent that binds to topoisomerase I
EXPERIMENTAL: Cohort 2; Patients with advanced or metastatic esophageal squamous cell carcinoma are to receive SHR-1210 with apatinib and paclitaxel liposome plus nedaplatin in cohort 2.	Drug: SHR-1210; a novel anti-PD-1 antibody; Drug: Apatinib; a VEGFR-2 tyrosine kinase inhibitor; Drug: Paclitaxel liposome; cytotoxic agent that prevent depolymerization of cellular microtubules; Drug: Nedaplatin; cytotoxic agent that cross-links and denatures strands of DNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	objective response rate of the patients in cohort 1 and cohort 2	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival (PFS)	progression-free survival (PFS) of the patients in cohort 1 and cohort 2	24 months
overall survival	overall survival of the patients in cohort 1 and cohort 2	24 months
treatment-related adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	24 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Publications and helpful links

General Publications

• Zhang B, Qi L, Wang X, Xu J, Liu Y, Mu L, Wang X, Bai L, Huang J. Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma. Cancer Commun (Lond). 2020 Dec;40(12):711-720. doi: 10.1002/cac2.12119. Epub 2020 Dec 12.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 31, 2018
• Primary Completion (ANTICIPATED): March 28, 2020
• Study Completion (ANTICIPATED): March 28, 2021

Study Registration Dates

• First Submitted: July 20, 2018
• First Submitted That Met QC Criteria: July 20, 2018
• First Posted (ACTUAL): July 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 9, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Neoplasms, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Topoisomerase I Inhibitors; Paclitaxel; Irinotecan; Apatinib; Nedaplatin
• Other Study ID Numbers: NCC201807010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No