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SHR-1210 Combined With Apatinib Mesylate in the Perioperative Treatment of Hepatocellular Carcinoma (HCC-009)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04297202
Recruitment Status : Recruiting
First Posted : March 5, 2020
Last Update Posted : August 7, 2020
Sponsor:
Collaborator:
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
The First Affiliated Hospital with Nanjing Medical University

Brief Summary:
This is a Phase II , Open-label , Investigator-initiated Trail of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With Apatinib in Patients With Hepatocellular Carcinoma(HCC).This study aims to evaluate the safety and efficacy of SHR-1210 combination with Apatinib as a preoperative treatment of HCC.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Apatinib Combined With SHR-1210 Injection Phase 2

Detailed Description:
This is an Open, Single Arm, Exploratory and Phase II Clinical Trial of Apatinib Combined With SHR-1210 (an Anti-PD-1 Inhibitor) in Patients With Hepatocellular Carcinoma(HCC) as Perioperative Treatment. we conduct this study in order to observe and evaluate the efficacy and safety of Apatinib combined with SHR-1210 (an Anti-PD-1 Inhibitor) in treatment of patients with HCC. Primary Efficacy Endpoint: Major pathologic response (MPR), Secondary Efficacy Endpoints: Pathological complete response Rate (pCR), Objective Response(ORR) (According to RECIST Version 1.1), Recurrence-free survival(RFS) and Overall survival rate of 6 months (OS %-6 m). Safety and tolerance will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.0.3.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-label, Single Arm, Investigator-initiated Trail of An Anti-PD-1 Inhibitor SHR-1210 in Combination With Apatinib in the Perioperative Treatment of Hepatocellular Carcinoma
Actual Study Start Date : December 1, 2019
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : December 1, 2021

Arm Intervention/treatment
Experimental: Apatinib Combined With SHR-1210 Injection

SHR-1210 Injection: 3 cycles of neoadjuvant therapy before surgery, two weeks is a treatment cycle; Apatinib : D1-D21 : 250 mg, orally, qd; Before surgery, the patient's surgical pathology samples still need to be collected.

D46 : Patients were preoperatively evaluated. Operable patients were scheduled for hepatectomy with/without microwave ablation;

After 4 to 8 weeks after liver resection, a postoperative adjuvant program is performed. The cycle of a three-week plan will be performed with a total of 8 cycles with the treatment of Apatinib combination with SHR-1210 Injection.

Drug: Apatinib Combined With SHR-1210 Injection

3 cycles of neoadjuvant therapy before surgery, two weeks is a treatment cycle: D1、D15、D31 : SHR-1210 200mg, I.V, q2w; D1-D20 : Apatinib 250 mg, orally, qd; D46 : Patients were preoperatively evaluated. Operable patients were scheduled for hepatectomy with/without microwave ablation; After 4 to 8 weeks after liver resection, a postoperative adjuvant program is performed. Three weeks is a treatment cycle with a total of 8 cycles

In each cycle:

D1: SHR-1210 200mg, I.V, q3w; D1-D21: Apatinib 250mg, orally, qd;





Primary Outcome Measures :
  1. Major pathologic response [ Time Frame: 6 months ]
    It is defined as residual tumors less than 10% after neo-adjuvant therapy


Secondary Outcome Measures :
  1. Pathological complete response [ Time Frame: 6 months ]
    No histologic evidence of malignancy or only the ingredients of carcinoma in situ was found in primary tumors

  2. Objective Response(ORR) [ Time Frame: Before surgery; ]
    It is defined as the proportion of patients whose tumors shrink to a predetermined size and maintain a minimum time limit. It includes the cases of CR and PR.

  3. Recurrence free survival(RFS) [ Time Frame: through study completion, an average of 1 year ]
    from surgery to relapse or death resulting from any cause .

  4. Recurrence free survival rates of 6 months and 12 months [ Time Frame: 12 months ]
    the rate of proportion of all patients from surgery to relapse or death resulting from any cause.

  5. Overall survival rate (6 m or 12 m) [ Time Frame: through study completion; the rate of OS for 6 months and 12 months ]
    It is defined as the time from randomization to death from any cause during the course of the study

  6. Safety as measured by the rate of AEs [ Time Frame: through study completion, an average of 1 year ]
    Safety will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 4.0.3



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The patient volunteered to participate in the study and signed an informed consent form
  2. ≥18 years of age,Male or female
  3. Subjects are diagnosed with histologically or cytologically confirmed HCC
  4. Subjects haven't received any systemic treatment for HCC before admission.
  5. Subjects enrolled must have measurable lesion(s) according to the RECIST 1.1 standard
  6. ECOG performance status of 0 or 1
  7. Life expectancy ≥ 12 weeks
  8. Subjects are diagnosed with resectable stage IIB, stage IIIA HCC cancer.
  9. The main organ's function is normal and it should meet the following criteria(Excludes use of any blood components and cell growth factors during the screening period)

    1. Absolute neutrophil count≥1.5×109 /L
    2. Platelets≥80×109/L ;Hemoglobin≥9.0 g/dL; Serum albumin≥3g/dL
    3. Thyroid stimulating hormone (TSH)≤1.0×upper limit of normal(ULN)(If abnormal, T3 and T4 levels should be examined at the same time)
    4. Total bilirubin (TBIL)≤1.5×upper limit of normal (ULN); ALT and AST≤1.5×upper limit of normal(ULN); AKP≤ 2.5×upper limit of normal(ULN)
    5. Serum creatinine ≤1.5×ULN or creatinine clearance > 60 mL/minute (using Cockcroft-Gault formula)

Exclusion Criteria:

  1. Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma; other active malignant tumor except HCC within 5 years or simultaneously
  2. Be ready for or previously received organ or allogenic bone marrow transplantation
  3. Moderate-to-severe ascites with clinical symptoms
  4. History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal hemorrhage.
  5. Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6 months prior to the start of study treatment.
  6. Known genetic or acquired hemorrhage or thrombotic tendency.
  7. The patient is currently using or has recently used (within 10 days before the start of study treatment) aspirin (> 325mg / day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel and cilostazol.
  8. Thrombosis or thromboembolic event within 6 months prior to the start of study treatment.
  9. Cardiac clinical symptom or disease that is not well controlled.
  10. Subjects have uncontrollable hypertension (systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg), despite patients have taken the best drug treatment ;Subjects have had a hypertensive crisis or hypertensive encephalopathy
  11. Patient develops severe vascular disease within 6 months before the start of study treatment.
  12. Patients with severe, unhealed or split wounds and active ulcers or untreated fractures
  13. Patients who underwent surgical treatment within 4 weeks prior to the start of study treatment.
  14. Factors to affect oral administration (such as patients unable to swallow oral medications, malabsorption syndrome etc. situations evidently affect drug absorption).
  15. Patients with gastrointestinal diseases such as intestinal obstruction (including incomplete intestinal obstruction) or those who may have caused gastrointestinal bleeding, perforation or obstruction.
  16. There is evidence of intragastric gas that cannot be explained by puncture or recent surgery.
  17. Previous or current presence of metastasis to central nervous system.
  18. Subjects have history of hepatic encephalopathy.
  19. The subject has an interstitial lung disease that is symptomatic or may interfere with the discovery or management of suspected drug-related lung toxicity; previous and current subjects with a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-associated pneumonia, severe impaired lung function, etc.
  20. The patient has any active autoimmune disease or a history of autoimmune disease expected relapse.
  21. Severe infection within 4 weeks prior to the start of study treatment.
  22. A history of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease.
  23. Prior therapy with any anti-PD-1/PD-L1 drug (specifically targeting T-cell co-stimulation or checkpoint pathways), Sorafenib or Apatinib.
  24. Subjects were vaccinated with live attenuated vaccine within 28 days before the first dose or expected to receive this vaccine within 60 days after the last dose or during the study period.
  25. Treatment of other investigational product(s) within 28 days prior to the start of study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04297202


Contacts
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Contact: Xuehao Wang 86-025-68303211 Wangxh@njmu.edu.cn

Locations
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China, Jiangsu
Jiangsu Province Hospital Recruiting
Nanjing, Jiangsu, China, 210029
Contact: Xuehao Wang    86-025-68303211    wangxh@njmu.edu.cn   
Sponsors and Collaborators
The First Affiliated Hospital with Nanjing Medical University
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Investigators
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Study Chair: Xuehao Wang The First Affiliated Hospital with Nanjing Medical University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: The First Affiliated Hospital with Nanjing Medical University
ClinicalTrials.gov Identifier: NCT04297202    
Other Study ID Numbers: 2019-SR-332
First Posted: March 5, 2020    Key Record Dates
Last Update Posted: August 7, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The First Affiliated Hospital with Nanjing Medical University:
Hepatocellular Carcinoma
the Perioperative Treatment
HCC
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Apatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action