Exploratory Clinical Study of Apatinib and SHR-1210 in Treating Advanced Hepatocellular Carcinoma or Gastric Cancer

NCT02942329 | Unknown Phase 1

• 1 other identifier: SHR-1210-APA-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to observe and preliminary explore the efficacy and safety of combination of Apatinib and SHR-1210 regimen in treating advanced hepatocellular carcinoma or gastric cancer. Apatinib is a small-molecule vascular endothelial growth factors receptor (VEGFR) tyrosine kinase inhibitor, similar to vatalanib (PTK787), but with a binding affinity 10 times that of vatalanib or sorafenib. SHR-1210 is a humanized anti-PD-1 monoclonal antibody.

Conditions

Gastric Cancer; Hepatocellular Carcinoma

Keywords

humanized anti-PD-1 monoclonal antibody; apatinib; Gastric Neoplasms; Gastric Cancer; Cancer of Stomach; Hepatocellular Carcinoma; Liver Cancer, Adult; Liver Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survival rate

  6 months and 12 months

  Up to approximately 12 months

Secondary Outcomes (4)

• Tumor response rate

  Up to approximately 12 months

• Disease control rate

  Up to approximately 12 months

• Duration of response

  Up to approximately 12 months

• Safety as measured by the rate of AEs, deaths and laboratory abnormalities (e.g. Grade 3 or higher per CTCAE v4 )

  From the first assignment of informed consent form up to 90 days after the last dose

Study Arms (1)

apatinib and SHR-1210

EXPERIMENTAL

Every patients will received apatinib orally every day and SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks until disease progression or intolerance of side effects.

Drug: apatinib; Drug: SHR-1210

Interventions

apatinib DRUG

Apatinib was administered 250mg or 375mg orally daily. For gastric cancer patients, the dose would be 250mg or 375mg daily. For hepatocellular carcinoma patients, the dose would be 250mg daily.

apatinib and SHR-1210

SHR-1210 DRUG

SHR-1210 was administered 200mg (3mg/kg for underweight patients) iv every 2 weeks.

apatinib and SHR-1210

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-70 years old, both genders.
• To be confirmed to meet the clinical diagnosis standard, histologically or cytologically confirmed with hepatocellular carcinoma or gastric cancer. Patients must be diagnosed with advanced disease(not eligible for surgical and/or locoregional therapies, or metastatic disease), disease progressed or refractory to standard therapies(had been intolerant to standard therapies, or had refused standard therapy), or lack of other effective treatment methods.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Life expectancy of at least 3 months.
• Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
• For patients with advanced hepatocellular carcinoma, liver function status Child-Pugh Class A or B (score\<=7).
• Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment)as determined by: Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L (for patients with advanced hepatocellular carcinoma), Platelet count ≥ 100×109/L (for patients with advanced gastric cancer); serum albumin ≥2.8 g/dL; serum total bilirubin (TBIL)≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal(ULN), for subjects with liver metastases, ALT and AST≤5×ULN; Calculated creatinine clearance (CrCl) \> 50 mL/min (Cockcroft-Gault formula will be used to calculate CrCl).
• Females of childbearing potential (FOCBP), who are not surgically sterile or postmenopausal, must conduct pregnancy test (serum or urine) within 7 days before enrollment, and must not be pregnant or breast-feeding women. If the result is negative, she must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs. And non-sterilized males who are sexually active must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs.
• Patients join the study voluntarily, sign a consent form, have good compliance, and comply with follow-up.

You may not qualify if:

• Patients must not have had prior treatment with SHR-1210 or any other PD-L1 or PD-1 antagonists, and must not have had be enrolled in the phase III Study of Apatinib After Systemic Therapy in Patients With Hepatocellular Carcinoma.
• Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
• Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed.
• Known history of hypersensitivity to any components of the SHR-1210 formulation, or other antibody formulation.
• Active central nervous system (CNS) metastases with clinical symptoms (including cerebral edema, steroid requirement, or progressive disease). Subjects with brain or meningeal metastases that were previously treated must be clinically stable (magnetic resonance imaging \[MRI\] at least 4 weeks apart do not show evidence of new or enlarging metastases) and have discontinued immunosuppressive doses of systemic steroids (\> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration.
• Patients with other malignant tumor (except cured skin basal cell carcinoma and cervical carcinoma).
• Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class \> 2), ventricular arrhythmia which need medical intervention, left ventricular ejection fraction(LVEF) \< 50%.
• Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents(within 3 months): systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg.
• Coagulation abnormalities (PT\>16s、APTT\>43s、TT\>21s、Fbg\<2g/L), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
• Prior systemic chemotherapy, radiotherapy, immunotherapy, hormone therapy, surgery or target therapy within 4 weeks (Or 5 half-life of the drug, calculate the longer ) before the study drug administration, or any unresolved AEs \> Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (with the exception of any stable chronic toxicities not expected to resolve).
• Patients with clinical symptoms of ascites or pleural effusion, need therapeutic puncture and drainage.
• Previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency, such as: esophageal varices, local active ulcerative lesions, gastric ulcer and duodenal ulcer, the ulcerous colitis, gastrointestinal diseases such as portal hypertension or resection of tumor with bleeding risk, etc.
• Patients with or previous with serious hemorrhage (bleeding \> 30 ml within 3 months), haemoptysis (\> 5 ml within 4 weeks) of thromboembolic events within 12 months (including stroke events and/or transient ischemic attack).
• Active infection or an unexplained fever \> 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled).
• Previous experience abdomen fistula, gastrointestinal perforation, or abdominal abscess within 4weeks.

Sponsors & Collaborators

• The Affiliated Hospital of the Chinese Academy of Military Medical Sciences: lead

Study Sites (1)

The Affiliated Hospital of the Chinese Academy of Military Medical Sciences

Beijing, Beijing Municipality, 100071, China

RECRUITING

Related Publications (1)

• Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q. Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study. Clin Cancer Res. 2019 Jan 15;25(2):515-523. doi: 10.1158/1078-0432.CCR-18-2484. Epub 2018 Oct 22.

  PMID: 30348638 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Carcinoma, Hepatocellular

Interventions

apatinib; camrelizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases

Study Officials

• Jian-Ming Xu, M.D.

  The Affiliated Hospital of the Chinese Academy of Military Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian-Ming Xu, M.D.

CONTACT

+861066947176; jmxu2003@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2016
• First Posted: October 24, 2016
• Study Start: October 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: February 26, 2018

Record last verified: 2018-01

Locations

CN (1)