- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03816553
SHR-1210 in Combination With Apatinib in Patients With Metastatic, Persistent, or Recurrent Cervical Cancer
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
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Guangdong
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Guangzhou, Guangdong, China, 510060
- Sun Yat-sen University Cancer Center
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Guangzhou, Guangdong, China, 511400
- Guangzhou Panyu Central Hospital
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Guanzhou, Guangdong, China, 510080
- The First Affiliated Hospital of Sun Yat-sen University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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;
- Age ≥ 18 years and ≤ 70 years;
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy exceeds 3 months;
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
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)
- Written informed consent.
Exclusion Criteria:
- Histopathologic diagnoses of tumors other than squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma.
- Participated in other clinical trials, or finish other clinical trials within 4 weeks.
- 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.
- Known history of hypersensitivity to any components of the SHR-1210 formulation, or other monoclonal antibody.
- 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.
- 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.
- 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.
- Arterial thrombus or phlebothrombosis within 6 months.
- Hypertension that can not be well controlled through antihypertensive drugs (systolic pressure ≥ 140 mm Hg and/or diastolic pressure ≥ 90 mm Hg)
- Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
- Coagulation abnormalities (INR>2.0、PT>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
- Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events (except for alopecia) due to a previously administered agent.
- Has known active central nervous system metastases.
- 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.
- Has an active infection requiring systemic therapy.
- History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
- Hepatitis B virus (HBV) >2000 IU/ml or DNA ≥ 1×10^4/ml; or hepatitis C virus (HCV) RNA ≥ 1×10^3/ml).
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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
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SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg (3mg/kg for underweight patients).
Other Names:
Apatinib will be administered 250mg orally, once daily until progression.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: Up to approximately 12 months
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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
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Up to approximately 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: Up to approximately 24 months
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Overall survival is defined as the duration from date of enrollment to the date of death from any cause.
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Up to approximately 24 months
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Duration of Response (DCR)
Time Frame: Up to approximately 24 months
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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.
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Up to approximately 24 months
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Duration of Response (DOR)
Time Frame: Up to approximately 24 months
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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.
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Up to approximately 24 months
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Progression-free Survival (PFS)
Time Frame: Up to approximately 24 months
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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
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Up to approximately 24 months
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6-month PFS rate
Time Frame: From date of enrollment up to 6 months
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The rate of 6-month PFS
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From date of enrollment up to 6 months
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9-month OS rate
Time Frame: From date of enrollment up to 9 months
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The rate of 9-month OS
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From date of enrollment up to 9 months
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Incidence of Adverse Events (AEs) in the treatment of SHR1210 in combination with apatinib
Time Frame: Up to approximately 24 months
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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.
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Up to approximately 24 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Baseline, every other cycle (each cycle is 28 days) and up to approximately 24 months
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Pain assessed by Brief Pain Inventory (BPI)
Time Frame: Baseline, every other cycle (each cycle is 28 days) and up to approximately 24 months
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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.
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Baseline, every other cycle (each cycle is 28 days) and up to approximately 24 months
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PD-L1 expression on tumor and immune cells
Time Frame: Up to approximately 24 months
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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.
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Up to approximately 24 months
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Tumor Mutation Burden (TMB)
Time Frame: Up to approximately 24 months
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The impact of TMB on efficacy of the combination of SHR-1210 and apatinib will be explored.
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Up to approximately 24 months
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Wang Y, Lai Y, Peng H, Yan S, Liu Z, Tong C, Huang X. Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial. Clin Transl Oncol. 2023 Jan;25(1):256-268. doi: 10.1007/s12094-022-02945-1. Epub 2022 Sep 17.
- Huang X, He M, Peng H, Tong C, Liu Z, Zhang X, Shao Y, Zhu D, Zhang J, Yin JC, Yang F, Lan C. Genomic profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: a secondary analysis of the CLAP trial. J Immunother Cancer. 2021 May;9(5):e002223. doi: 10.1136/jitc-2020-002223. Erratum In: J Immunother Cancer. 2022 Feb;10(2):
- Lan C, Shen J, Wang Y, Li J, Liu Z, He M, Cao X, Ling J, Huang J, Zheng M, Zou G, Yan H, Liu Q, Yang F, Wei W, Deng Y, Xiong Y, Huang X. Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial. J Clin Oncol. 2020 Dec 1;38(34):4095-4106. doi: 10.1200/JCO.20.01920. Epub 2020 Oct 14.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Cervical Diseases
- Uterine Diseases
- Disease Attributes
- Uterine Cervical Neoplasms
- Recurrence
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Apatinib
Other Study ID Numbers
- B2018-169-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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