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Peramprizumab Combined With GP ± Anlotinib as Neoadjuvant Therapy in Locoregionally Advanced Nasopharyngeal Carcinoma

Primary Purpose

Nasopharyngeal Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
GP+Peramprizumab+Anlotinib
GP+Peramprizumab
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Voluntary participation with Written informed consent.
  2. Age ≥ 18 years and ≤ 65 years, male or non-pregnant female.
  3. Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III).
  4. Original clinical staged as III-IVa (according to the 8th AJCC edition),exclude T3-4N0, T3N1(Only retropharyngeal lymph nodes metastasized), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
  5. White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
  6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) .
  7. Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.

Exclusion Criteria:

  1. Patients with recurrent or metastatic nasopharyngeal carcinoma.
  2. Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
  3. Prior therapy with Systemic chemotherapy.
  4. Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
  5. Seropositivity for human immunodeficiency virus (HIV).
  6. Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
  7. Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
  8. Patients with immunodeficiency disease or a history of organ transplantation.
  9. Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressants within 4 weeks.
  10. Patients with severe dysfunction of heart, liver, lung, kidney or marrow.
  11. Patients with severe, uncontrolled disease or infections.
  12. Received other research drugs or in other clinical trials at the same time.
  13. Refuse or fail to sign the informed consent .
  14. Patients with other treatment contraindications.
  15. Patients with personality or mental disorders, incapacity or limited capacity for civil conduct.
  16. Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV deoxyribonucleic acid (HBV DNA) ≥1000cps/ml.
  17. Patients with positive HCV antibody test will only be enrolled in this study if the PCR test for HCV RNA is negative.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    GP combine with peramprizumab and anlotinib neoadjuvant therapy+CCRT+peramprizumab adjuvant therapy

    GP combine with Peramprizumab neoadjuvant therapy+CCRT+Peramprizumab adjuvant therapy

    Arm Description

    Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on days 1,8) , cisplatin (80mg per square meter on day 1), peramprizumab (200mg, day1), and anlotinib (10mg days 1-14) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT) ,then followed by adjuvant therapy with peramprizumab (200mg) every three weeks for a maximum of nine cycles after radiotherapy.

    Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on days 1,8) , cisplatin (80mg per square meter on day 1), peramprizumab (200mg, day1) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT) ,then followed by adjuvant therapy with peramprizumab (200mg) every three weeks for a maximum of nine cycles after radiotherapy.

    Outcomes

    Primary Outcome Measures

    Stage 1(Pick the Winner Study): Complete Response
    The proportion of patients who had a complete response was defined as those with all pathological cervical lymph nodes being less than 10 mm in the short axis and no unequivocal soft tissue mass in the local region. Disease response was evaluatedby by the Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) 95% confidence intervals (CIs) were calculated using the Clopper Pearson method
    Stage 2 (Cohort Expansion Study): Failure-free survival (FFS)
    Defined as the time from registration to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.

    Secondary Outcome Measures

    Overall survival (OS)
    Defined as the time from registration to death from any cause or censored at the date of last follow-up.
    Locoregional failure-free survival (LRRFS)
    Defined as the time from registration to local or regional relapse, or death from any cause.
    Distant metastasis-free survival (DMFS)
    Defined as the time from registration to distant metastasis, or death from any cause.
    Incidence rate of adverse events (AEs)
    Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events (acute toxicity) and late radiation toxicities were assessed by CTCAE v5.0.
    Objective Response Rate (ORR)
    Objective response rate (ORR) was assessed by the site Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) and was defined as the percentage of patients with a confirmed overall response of complete response (CR) or partial response (PR) and was based on all treated patients who had measurable disease at baseline (Day 1). 95% confidence intervals (CIs) were calculated using the Clopper Pearson method.

    Full Information

    First Posted
    January 11, 2022
    Last Updated
    January 14, 2022
    Sponsor
    Sun Yat-sen University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05193617
    Brief Title
    Peramprizumab Combined With GP ± Anlotinib as Neoadjuvant Therapy in Locoregionally Advanced Nasopharyngeal Carcinoma
    Official Title
    Peramprizumab Combined With GP ± Arotinib Induction Therapy + Concurrent Chemoradiotherapy + Adjuvant Peramprizumab in Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 20, 2022 (Anticipated)
    Primary Completion Date
    January 1, 2024 (Anticipated)
    Study Completion Date
    January 1, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Sun Yat-sen University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to explore the efficacy and safety of a combination of GP chemotherapy and Peramprizumab ± Anlotinib in neoadjuvant therapy combined with Peramprizumab in adjuvant therapy of locoregionally advanced nasopharyngeal carcinoma patients.
    Detailed Description
    Radiotherapy combined with chemotherapy is the standard treatment method for locally advanced NPC. In the 2020 National Comprehensive Cancer Network (NCCN) guidelines, GP regimen induction chemotherapy combined with concurrent chemoradiotherapy has been established as evidence-based grade 2A. Based on the results of phase 3 clinical trials, the addition of PD-1 monoclonal antibody to GP chemotherapy as a first-line treatment for patients with recurrent or metastatic nonkeratinizing NPC provided superior PFS, ORR and DoR than GP alone while maintaining a manageable safety profile. Therefore, the combination of PD-1 monoclonal antibody in GP induction chemotherapy may further improve the prognosis of patients with locally advanced NPC. There is a complex interaction between tumor immune microenvironment and tumor vascular remodeling. Anti-PD-1 monoclonal antibody combined with anti-VEGF have synergistic effect and inhibit tumor growth. Peramprizumab is a new type of PD-1 monoclonal antibody. It has the characteristics of strong antigen binding and slow dissociation rate, which can maintain the antitumor activity of T cells. Anlotinib is a multi-target tyrosine kinase inhibitor (TKI). It can effectively inhibit a variety of receptors, including vascular endothelial growth factor receptor (VEGFR), and block tumor angiogenesis more comprehensively. Based on the above research background, this study adopts a two-stage design: Stage I (Pick the Winner Study): For patients with locally advanced NPC, the complete response rate (CR) of tumor after induction chemotherapy was compared between the two groups of patients receiving GP + peramprizumab and GP + peramprizumab + arotinib before radiotherapy. The regimen with higher CR rate was the winner at this stage. Stage II ( Cohort Expansion Study): The 3-year failure free survival (FFS) of patients in the winning regimen of expansion cohort was calculated through long-term follow-up and compared with the data in previous trials.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Nasopharyngeal Carcinoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    104 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    GP combine with peramprizumab and anlotinib neoadjuvant therapy+CCRT+peramprizumab adjuvant therapy
    Arm Type
    Experimental
    Arm Description
    Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on days 1,8) , cisplatin (80mg per square meter on day 1), peramprizumab (200mg, day1), and anlotinib (10mg days 1-14) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT) ,then followed by adjuvant therapy with peramprizumab (200mg) every three weeks for a maximum of nine cycles after radiotherapy.
    Arm Title
    GP combine with Peramprizumab neoadjuvant therapy+CCRT+Peramprizumab adjuvant therapy
    Arm Type
    Active Comparator
    Arm Description
    Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on days 1,8) , cisplatin (80mg per square meter on day 1), peramprizumab (200mg, day1) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT) ,then followed by adjuvant therapy with peramprizumab (200mg) every three weeks for a maximum of nine cycles after radiotherapy.
    Intervention Type
    Drug
    Intervention Name(s)
    GP+Peramprizumab+Anlotinib
    Other Intervention Name(s)
    GP+AK105+AL3818
    Intervention Description
    GP combine with peramprizumab and anlotinib neoadjuvant therapy+CCRT+peramprizumab adjuvant therapy
    Intervention Type
    Drug
    Intervention Name(s)
    GP+Peramprizumab
    Other Intervention Name(s)
    GP+AK105
    Intervention Description
    GP combine with peramprizumab neoadjuvant therapy+CCRT+peramprizumab adjuvant therapy
    Primary Outcome Measure Information:
    Title
    Stage 1(Pick the Winner Study): Complete Response
    Description
    The proportion of patients who had a complete response was defined as those with all pathological cervical lymph nodes being less than 10 mm in the short axis and no unequivocal soft tissue mass in the local region. Disease response was evaluatedby by the Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) 95% confidence intervals (CIs) were calculated using the Clopper Pearson method
    Time Frame
    9 weeks
    Title
    Stage 2 (Cohort Expansion Study): Failure-free survival (FFS)
    Description
    Defined as the time from registration to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.
    Time Frame
    3 years
    Secondary Outcome Measure Information:
    Title
    Overall survival (OS)
    Description
    Defined as the time from registration to death from any cause or censored at the date of last follow-up.
    Time Frame
    3 years
    Title
    Locoregional failure-free survival (LRRFS)
    Description
    Defined as the time from registration to local or regional relapse, or death from any cause.
    Time Frame
    3 years
    Title
    Distant metastasis-free survival (DMFS)
    Description
    Defined as the time from registration to distant metastasis, or death from any cause.
    Time Frame
    3 years
    Title
    Incidence rate of adverse events (AEs)
    Description
    Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events (acute toxicity) and late radiation toxicities were assessed by CTCAE v5.0.
    Time Frame
    3 years
    Title
    Objective Response Rate (ORR)
    Description
    Objective response rate (ORR) was assessed by the site Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) and was defined as the percentage of patients with a confirmed overall response of complete response (CR) or partial response (PR) and was based on all treated patients who had measurable disease at baseline (Day 1). 95% confidence intervals (CIs) were calculated using the Clopper Pearson method.
    Time Frame
    9 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Voluntary participation with Written informed consent. Age ≥ 18 years and ≤ 65 years, male or non-pregnant female. Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III). Original clinical staged as III-IVa (according to the 8th AJCC edition),exclude T3-4N0, T3N1(Only retropharyngeal lymph nodes metastasized), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) . Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value. Exclusion Criteria: Patients with recurrent or metastatic nasopharyngeal carcinoma. Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx. Prior therapy with Systemic chemotherapy. Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures. Seropositivity for human immunodeficiency virus (HIV). Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix). Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies. Patients with immunodeficiency disease or a history of organ transplantation. Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressants within 4 weeks. Patients with severe dysfunction of heart, liver, lung, kidney or marrow. Patients with severe, uncontrolled disease or infections. Received other research drugs or in other clinical trials at the same time. Refuse or fail to sign the informed consent . Patients with other treatment contraindications. Patients with personality or mental disorders, incapacity or limited capacity for civil conduct. Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV deoxyribonucleic acid (HBV DNA) ≥1000cps/ml. Patients with positive HCV antibody test will only be enrolled in this study if the PCR test for HCV RNA is negative.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hai-Qiang Mai, Ph.D
    Phone
    8613570027338
    Email
    maihq@sysucc.org.cn
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Hai-Qiang Mai, Ph.D
    Organizational Affiliation
    Sun Yat-sen University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    31150573
    Citation
    Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.
    Results Reference
    background
    PubMed Identifier
    34341578
    Citation
    Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2. Erratum In: Nat Med. 2022 Jan;28(1):214.
    Results Reference
    background

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    Peramprizumab Combined With GP ± Anlotinib as Neoadjuvant Therapy in Locoregionally Advanced Nasopharyngeal Carcinoma

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