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

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: NCT03816553
Recruitment Status : Active, not recruiting
First Posted : January 25, 2019
Last Update Posted : September 28, 2021
Sponsor:
Information provided by (Responsible Party):
Xin Huang, Sun Yat-sen University

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.

Condition or disease Intervention/treatment Phase
Recurrent Cervical Carcinoma Metastatic Cervical Cancer Drug: SHR-1210 Drug: Apatinib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 49 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 19, 2019
Actual Primary Completion Date : April 30, 2020
Estimated Study Completion Date : August 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

Arm Intervention/treatment
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
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 6-month PFS rate [ Time Frame: From date of enrollment up to 6 months ]
    The rate of 6-month PFS

  4. 9-month OS rate [ Time Frame: From date of enrollment up to 9 months ]
    The rate of 9-month OS

  5. 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.

  6. 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.

  7. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT03816553


Locations
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China, Guangdong
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China, 510060
Guangzhou Panyu Central Hospital
Guangzhou, Guangdong, China, 511400
The First affiliated Hospital of Sun Yat-sen University
Guanzhou, Guangdong, China, 510080
Sponsors and Collaborators
Sun Yat-sen University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Xin Huang, Professor, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT03816553    
Other Study ID Numbers: B2018-169-01
First Posted: January 25, 2019    Key Record Dates
Last Update Posted: September 28, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Apatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action