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SHR-1210 in Combination With Apatinib in Patients With Metastatic, Persistent, or Recurrent Cervical Cancer

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ClinicalTrials.gov Identifier: NCT03816553
Recruitment Status : Active, not recruiting
First Posted : January 25, 2019
Last Update Posted : November 27, 2020
Sponsor:
Information provided by (Responsible Party):
Xin Huang, Sun Yat-sen University

Tracking Information
First Submitted Date  ICMJE January 13, 2019
First Posted Date  ICMJE January 25, 2019
Last Update Posted Date November 27, 2020
Actual Study Start Date  ICMJE January 19, 2019
Actual Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2019)
Objective Response Rate (ORR) [ Time Frame: Up to approximately 12 months ]
ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2019)
  • Progression-free Survival (PFS) [ Time Frame: Up to approximately 24 months ]
    Progression-free survival is defined as the duration from date of enrollment to the first occurrence of progression of disease or death from any cause
  • Overall survival (OS) [ Time Frame: Up to approximately 24 months ]
    Overall survival is defined as the duration from date of enrollment to the date of death from any cause.
  • 6-month PFS rate [ Time Frame: From date of enrollment up to 6 months ]
    The rate of 6-month PFS
  • 9-month OS rate [ Time Frame: From date of enrollment up to 9 months ]
    The rate of 9-month OS
  • Duration of Response (DCR) [ Time Frame: Up to approximately 24 months ]
    DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease (SD) per RECIST 1.1.
  • Duration of Response (DOR) [ Time Frame: Up to approximately 24 months ]
    DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
  • Incidence of Adverse Events (AEs) in the treatment of SHR1210 in combination with apatinib [ Time Frame: Up to approximately 24 months ]
    Number of participants with adverse events occurring up to 30 days after the last administration are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 24, 2019)
  • Impact of the treatment on Quality of Life (QOL) measured by the Functional Assessment of Cancer Therapy (FACT)-Cervical Trial Outcome of Index (FACT-Cx TOI) [ Time Frame: Baseline, every other cycle (each cycle is 28 days) and up to approximately 24 months ]
    The FACT-Cx TOI is a scale for assessing general QOL of cervical cancer patients consisting of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Cervical Cancer subscale (15 items). Each item in the FACT-Cx TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements (or questions), reversal was performed prior to score calculation. The score ranges 0-116 with a large score suggesting better QOL.
  • Pain assessed by Brief Pain Inventory (BPI) [ Time Frame: Baseline, every other cycle (each cycle is 28 days) and up to approximately 24 months ]
    Single item from the BPI assessing "worst pain" in the past 24 hours, on a 0-10 scale with a higher score indicating more pain than a low score.
  • PD-L1 expression on tumor and immune cells [ Time Frame: Up to approximately 24 months ]
    The efficacy of the combination of SHR-1210 and apatinib as measured by objective response, will be described in patients according to PD-L1 positive and PD-L1 negative.
  • Tumor Mutation Burden (TMB) [ Time Frame: Up to approximately 24 months ]
    The impact of TMB on efficacy of the combination of SHR-1210 and apatinib will be explored.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE SHR-1210 in Combination With Apatinib in Patients With Metastatic, Persistent, or Recurrent Cervical Cancer
Official Title  ICMJE SHR-1210, a Novel Anti-pd-1 Antibody, in Combination With Apatinib in Patients With Metastatic, Persistent, or Recurrent Cervical Cancer: a Single-arm, Open Label, Multi-center, Phase II Study
Brief Summary The purpose of this study is to explore the efficacy and safety of SHR-1210 in combination with apatinib in treating patients with metastatic, persistent, or recurrent cervical cancer.
Detailed Description SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1). Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) selectively inhibits Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2). Patients with metastatic, persistent, or recurrent cervical cancer who failed to first-line chemotherapy +/- bevacizumab will received SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks and apatinib 250mg orally once daily. The efficacy and safety will be observed.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Cervical Carcinoma
  • Metastatic Cervical Cancer
Intervention  ICMJE
  • Drug: SHR-1210
    SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg (3mg/kg for underweight patients).
    Other Name: Camrelizumab
  • Drug: Apatinib
    Apatinib will be administered 250mg orally, once daily until progression.
    Other Name: Apatinib Mesylate
Study Arms  ICMJE Experimental: SHR-1210 + Apatinib
Participants receive SHR-1210 200mg (3mg/kg for underweight patients) intravenously every 2 weeks and apatinib 250mg orally once daily until disease progression or unacceptable toxicity
Interventions:
  • Drug: SHR-1210
  • Drug: Apatinib
Publications *

*   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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 24, 2019)
49
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 1, 2021
Actual Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients must have metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy;
  2. Age ≥ 18 years and ≤ 70 years;
  3. Patients must have measurable disease per RECIST 1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI),; a lymph node must be ≥ 15 mm in short axis. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Life expectancy exceeds 3 months;
  6. Patients must have had at least one prior systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix.

    Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix; adjuvant therapy includes cisplatin given concurrent with primary radiation therapy (CCRT) and adjuvant chemotherapy given following the completion of concurrent chemotherapy and radiation therapy

  7. Patients must have adequate organ function

    • Absolute neutrophil count (ANC) ≥ 1.5×10^9/L
    • Platelet count ≥ 80 × 10^9/L
    • Hemoglobin ≥ 90 g/L
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
    • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 × ULN may be enrolled)
    • Creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula)
    • Baseline albumin ≥ 28 g/L
    • Thyroid-stimulating hormone (TSH) levels ≤ 1 × ULN (however, patients with free Triiodothyronine [FT3] or free Thyroxine [FT4] levels ≤ 1 × ULN may be enrolled)
  8. Written informed consent.

Exclusion Criteria:

  1. Histopathologic diagnoses of tumors other than squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma.
  2. Participated in other clinical trials, or finish other clinical trials within 4 weeks.
  3. Prior exposure to immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 antibodies, or prior exposure to apatinib.
  4. Known history of hypersensitivity to any components of the SHR-1210 formulation, or other monoclonal antibody.
  5. 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.
  6. 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.
  7. Clinically significant cardiovascular diseases, including but not limited to congestive heart failure (New York heart association (NYHA) class > 2), unstable or severe angina, severe acute myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.
  8. Arterial thrombus or phlebothrombosis within 6 months.
  9. Hypertension that can not be well controlled through antihypertensive drugs (systolic pressure ≥ 140 mm Hg and/or diastolic pressure ≥ 90 mm Hg)
  10. Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
  11. Coagulation abnormalities (INR>2.0、PT>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
  12. Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events (except for alopecia) due to a previously administered agent.
  13. Has known active central nervous system metastases.
  14. Patients with a prior invasive malignancy who have had any evidence of disease within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  15. Has an active infection requiring systemic therapy.
  16. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
  17. Hepatitis B virus (HBV) >2000 IU/ml or DNA ≥ 1×10^4/ml; or hepatitis C virus (HCV) RNA ≥ 1×10^3/ml).
  18. Has received a live vaccine within 4 weeks prior to the first dose of trial treatment. Note: Injection of inactivated viral vaccines against seasonal influenza are allowed.
  19. Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 75 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 NCT03816553
Other Study ID Numbers  ICMJE B2018-169-01
Has Data Monitoring Committee Yes
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 Xin Huang, Sun Yat-sen University
Study Sponsor  ICMJE Sun Yat-sen University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sun Yat-sen University
Verification Date November 2020

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