Clinical Trials /

ADjuVant Apatinib in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy

NCT02874651

Description:

This study will enroll patients with non-metastatic nasopharyngeal carcinoma (NPC) that have residual Epstein-Barr virus (EBV) DNA after curative radiotherapy or chemoradiotherapy. The purpose is to evaluate the survival in these patients treated with apatinib (YN968D1), an inhibitor of vascular endothelial growth factor receptor (phase IIa) and to compare the survival in these patients treated with apatinib versus placebo (phase IIb).

Related Conditions:
  • Nasopharyngeal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: ADjuVant Apatinib in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy
  • Official Title: ADjuVant Apatinib in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy With or Without Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: Ahead-N301
  • NCT ID: NCT02874651

Conditions

  • Nasopharyngeal Neoplasms

Interventions

DrugSynonymsArms
ApatinibYN968D1Apatinib
PlaceboPlacebo tabletPlacebo

Purpose

This study will enroll patients with non-metastatic nasopharyngeal carcinoma (NPC) that have residual Epstein-Barr virus (EBV) DNA after curative radiotherapy or chemoradiotherapy. The purpose is to evaluate the survival in these patients treated with apatinib (YN968D1), an inhibitor of vascular endothelial growth factor receptor (phase IIa) and to compare the survival in these patients treated with apatinib versus placebo (phase IIb).

Detailed Description

      This study has two parts. In the single arm phase IIa part, we will enroll 25 patients that
      have residual Epstein-Barr virus (EBV) DNA after curative radiotherapy or chemoradiotherapy.
      All patients will receive apatinib. The purpose is to evaluate the disease free-survival
      (DFS) in these patients treated with apatinib. In the phase IIb part, patients will be
      randomized to apatinib or placebo in a ratio of 1:1. The estimated sample size is 78 in phase
      IIb. However, the final sample size in phase IIb will be determined based on results of the
      phase IIa part.
    

Trial Arms

NameTypeDescriptionInterventions
ApatinibExperimentalIn the phase IIb part of this trial, patients in this arm will take oral apatinib until disease progression, intolerable toxicity, death or to a maximum of 2 years.
  • Apatinib
PlaceboPlacebo ComparatorIn the phase IIb part of this trial, patients in this arm will take oral placebo until disease progression, intolerable toxicity, death or to a maximum of 2 years.
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          1. Biopsy proven nasopharyngeal carcinoma, with detectable pretreatment plasma EBV DNA

          2. Have detectable plasma EBV DNA at the end of (+/- 1 week) curative radiotherapy or
             chemoradiotherapy (radiation dose > 66Gy), determined by the central lab

          3. No clinical evidence of persistent loco-regional disease

          4. No evidence of distant metastasis, based upon skeletal scintigraphy, chest X-ray
             examination, and liver ultrasound or other appropriate workup (e.g., CT, MRI or
             positron emission tomography (PET)/CT]) within 21 days prior to registration

          5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          6. Anticipated survival >= 3 months

          7. Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

          8. Platelets > 80,000 cells/mm^3

          9. Hemoglobin >= 8.0 g/dl (no transfusion within the last 14 days)

         10. Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)

         11. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x
             institutional ULN

         12. Creatinine clearance (CC) >= 50 ml/min estimated by Cockcroft-Gault formula

        Exclusion Criteria:

          1. Patients with stage III-IV disease (American Joint Committee On Cancer/Union for
             International Cancer Control 7th) and no contraindication to chemotherapy that didn't
             receive platinum based concurrent chemotherapy during radiation

          2. Patients with tumor possibly invaded main vessels (e.g. encasement of the internal
             jugular artery/vein) at diagnosis; or tumor that, in the judgment of the investigator,
             likely to invade main vessels and cause life-threatening hemorrhage events during
             study

          3. History of serious hemorrhage events or grade 3 or higher hemorrhage within 4 weeks
             prior to registration

          4. Hypertension that couldn't be well controlled with single medication; unstable angina;
             angina diagnosed within the last 3 months; myocardial infarction within the last 6
             months; cardiac arrhythmia that need long-term medication; grade 2 or higher cardiac
             dysfunction (NYHA)

          5. Proteinuria

          6. Coagulation dysfunction or predisposition to hemorrhage; on treatment of
             anticoagulation medication or vitamin K antagonist; low dose warfarin (1mg po qd) or
             aspirin (less than 100mg daily) were permitted as long as the international normalized
             ratio (INR) = < 1.5

          7. Thrombosis within the last 1 year, except cured vein thrombosis related to vein
             indwelling catheter

          8. Unhealed bone fracture or chronic unhealed wound

          9. Illness that would interfere with oral medication, including dysphagia, chronic
             diarrhea, or ileus

         10. Pregnant or lactating women

         11. Women of childbearing potential and men who are sexually active and not willing/able
             to use medically acceptable forms of contraception during and within 6 months after
             study

         12. Current drug abuse or mentally disabled

         13. History of congenital or acquired immune deficiency disease or organ transplantation

         14. Major medical illness, which in the investigator's opinion would endanger the patients
             or interfere with the completion of therapy and follow up
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease-free survival
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:overall survival
Time Frame:5 years
Safety Issue:
Description:
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:2 years
Safety Issue:
Description:
Measure:Changes in quality of life (QOL) as assessed by EORTC QLQ-C30
Time Frame:2 years
Safety Issue:
Description:
Measure:Distance Metastasis Free Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:locoregional relapse free survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Correlation of plasma EBV DNA load with the effect of apatinib on survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Correlation of pretreatment serum VEGF level with the effect of apatinib on survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Correlation of pretreatment serum VEGFR-2 level with the effect of apatinib on survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Correlation of adverse event (hypertension) with the effect of apatinib on survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Correlation of adverse event (hand-foot syndrome) with the effect of apatinib on survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Correlation of the change from baseline in serum VEGF level at 4 weeks with the effect of apatinib on survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Correlation of the change from baseline in serum VEGFR-2 level at 4 weeks with the effect of apatinib on survival
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sun Yat-sen University

Trial Keywords

  • Nasopharyngeal Carcinoma
  • EB Virus
  • DNA
  • vascular endothecial growth factor receptor inhibitor
  • Apatinib

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