Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung Cancer(NSCLC)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03083041
Recruitment Status : Unknown
Verified March 2017 by Jiangsu HengRui Medicine Co., Ltd..
Recruitment status was:  Recruiting
First Posted : March 17, 2017
Last Update Posted : February 7, 2018
Sponsor:
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.

Tracking Information
First Submitted Date  ICMJE March 2, 2017
First Posted Date  ICMJE March 17, 2017
Last Update Posted Date February 7, 2018
Actual Study Start Date  ICMJE March 22, 2017
Estimated Primary Completion Date December 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2017)
  • Part 1: Incidence and grade of adverse events (AEs) and Serious adverse events (SAEs) [ Time Frame: up to 24 weeks ]
    AEs and SAEs assessed by NCI-CTCAE v4.03
  • Part 2:Objective response rate (ORR) per RECIST 1.1 [ Time Frame: Up to approximately 6 months ]
    ORR is defined as the proportion of subjects who have achieved complete response (CR) or partial response (PR) according to RECIST 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2017)
  • Part 1: Apatinib plasma concentrations and serum SHR-1210 concentrations [ Time Frame: Cycles 1-2(each cycle is 28 days) ]
    Apatinib plasma concentrations and serum SHR-1210 concentrations in Expansion cohort
  • Part 1:Peak Plasma Concentration (Cmax) of Apatinib and SHR-1210 [ Time Frame: Cycles 1-2(each cycle is 28 days) ]
    Cmax of Apatinib and SHR-1210 in Expansion cohort
  • Part 1:Objective response rate (ORR) - RECIST 1.1 [ Time Frame: Up to approximately 6 months ]
    ORR is defined as the proportion of subjects who have achieved complete response (CR) or partial response (PR) according to RECIST 1.1
  • Duration of Response (DoR) [ Time Frame: Up to approximately 2 years ]
    Duration of Response (DoR) per RECIST 1.1
  • Progression-free survival(PFS) [ Time Frame: Up to approximately 2 years ]
    PFS per RECIST 1.1
  • Overall survival rate at 12 months (OSR12) [ Time Frame: Up to approximately 1 years ]
    OSR12 will be calculated based on Kaplan-Meier estimates of Overall survival at 12 months
  • Part 1: Area under the plasma concentration-time curve from time 0 to 24 hrs, AUC[0-24] [ Time Frame: Cycles 1-2(each cycle is 28 days) ]
    AUC[0-24] of Apatinib and SHR-1210 in Expansion cohort
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung Cancer(NSCLC)
Official Title  ICMJE A Phase II Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung
Brief Summary

This is a multi-center, open-label, Phase II study of intravenous (IV) SHR-1210 at 200mg,q2w in combination with Apatinib at two dose levels in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC).

The study is composed of two parts. Part 1 of the study will determine the safety ,tolerability and pharmacokinetics of SHR-1210 in combination with Apatinib.

Part 2 includes a randomized comparison of Apatinib 250mg/d or 500mg/d plus SHR-1210 .

Subject's tumors will be screened at baseline for EGFR mutations, EML4-ALK translocation, and PD-L1 expression.But positive tumor PD-L1 expression will not be required for enrollment.

Detailed Description SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1). Apatinib is a new kind of selective Vascular Endothelial Growth Factor Receptor 2(VEGFR-2) tyrosine kinase inhibitor (TKI). A disease-control rate of 61.1% and a mPFS of 4.7 months were showed in Apatinib phase II study in patients with NSCLC.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Biological: SHR-1210
    SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg
  • Drug: Apatinib
    Apatinib tablet will be administered orally,once daily until progression
    Other Name: Apatinib Mesylate
Study Arms  ICMJE
  • Experimental: SHR-1210,200mg,q2w plus apatinib 250mg/d
    SHR-1210 200mg, IV, Q2W and Apatinib 250mg, PO, QD
    Interventions:
    • Biological: SHR-1210
    • Drug: Apatinib
  • Experimental: SHR-1210,200mg,q2w plus apatinib 500mg/d
    SHR-1210 200mg, IV, Q2W and Apatinib 500mg, PO, QD
    Interventions:
    • Biological: SHR-1210
    • Drug: Apatinib
  • Experimental: SHR-1210,200mg,q2w plus apatinib 375mg/d
    SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
    Interventions:
    • Biological: SHR-1210
    • Drug: Apatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: March 13, 2017)
118
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2019
Estimated Primary Completion Date December 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subjects >/= 18 years and </=70 years of age at the time of Informed Consent.
  2. Advanced relapsed or refractory predominantly NSCLC with at least one measurable lesion according to RECIST 1.1.
  3. Failure of second line of chemotherapy(Part 1);Failure of First line of chemotherapy(Part 2)
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  5. Patients must have recovered from any AEs of prior treatments before randomization.
  6. Adequate bone marrow,liver and renal function as assessed by the following laboratory tests conducted within 1 week before randomization. HB ≥ 90g/L; ANC≥1.5×10E+9/L; PLT≥100×10E+9/L; ALT and AST < 1.5×ULN; TBIL ≤1×ULN; Cr ≤1.5×ULN or CL≥60 ml/min.
  7. Life expectancy of at least three months.
  8. Male or female participants of childbearing potential must be willing to use an adequate method of contraception starting with the first dose of study drug through 60 days for female subjects and 120 days for male subjects after the last dose of study drug.
  9. Written informed consent and the willingness and ability to comply with all aspects of the protocol.

Exclusion Criteria:

  1. Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female≥ 470 ms).
  2. Severe or uncontrolled systemic disease such as clinically significant hypertension(systolic pressure >/= 140 mm Hg and/or diastolic pressure >/= 90 mm Hg), and Grade III-IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF<50%.
  3. Factors to affect oral administration(inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction).
  4. Coagulation disfunction,hemorrhagic tendency or receiving anticoagulant therapy
  5. >/= CTCAE 2 pneumorrhagia or >/= CTCAE 3 hemorrhage in other organs within 4 weeks.
  6. Bone fracture or wounds that was not cured.
  7. Arterial thrombus or phlebothrombosis within 6 months and taking anticoagulant agents.
  8. Mental diseases and psychotropic substances abuse.
  9. Previous treatment with an trial agent within 4 weeks
  10. Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
  11. Other coexisting malignant disease (except basal-cell carcinoma and carcinoma in situ of uterine cervix).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03083041
Other Study ID Numbers  ICMJE SHR-1210-APTN-II-202-NSCLC
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Jiangsu HengRui Medicine Co., Ltd.
Study Sponsor  ICMJE Jiangsu HengRui Medicine Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Jiangsu HengRui Medicine Co., Ltd.
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP