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

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ClinicalTrials.gov Identifier: NCT02874651
Recruitment Status : Recruiting
First Posted : August 22, 2016
Last Update Posted : November 1, 2016
Sponsor:
Collaborators:
First People's Hospital of Foshan
Guilin Medical University, China
Information provided by (Responsible Party):
Jun Ma, MD, Sun Yat-sen University

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Nasopharyngeal Neoplasms Drug: Apatinib Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 103 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ADjuVant Apatinib in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy With or Without Chemotherapy
Study Start Date : October 2016
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Apatinib
In 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.
Drug: Apatinib
Patients will take oral apatinib. The initial dose is 500 mg once daily. 28 days as one cycle. After 1 cycle, the dose will be escalated to 750 mg once daily in patients with good tolerance. Dose interruption or reduction is permitted in case of adverse events per protocol.
Other Name: YN968D1

Placebo Comparator: Placebo
In 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.
Drug: Placebo
Patients will take oral placebo. The initial dose is 500 mg once daily. 28 days as one cycle. After 1 cycle, the dose will be escalated to 750 mg once daily in patients with good tolerance. Dose interruption or reduction is permitted in case of adverse events per protocol.
Other Name: Placebo tablet




Primary Outcome Measures :
  1. Disease-free survival [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. overall survival [ Time Frame: 5 years ]
  2. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]
  3. Changes in quality of life (QOL) as assessed by EORTC QLQ-C30 [ Time Frame: 2 years ]
  4. Distance Metastasis Free Survival [ Time Frame: 2 years ]
  5. locoregional relapse free survival [ Time Frame: 2 years ]
  6. Correlation of plasma EBV DNA load with the effect of apatinib on survival [ Time Frame: 2 years ]
  7. Correlation of pretreatment serum VEGF level with the effect of apatinib on survival [ Time Frame: 2 years ]
  8. Correlation of pretreatment serum VEGFR-2 level with the effect of apatinib on survival [ Time Frame: 2 years ]
  9. Correlation of adverse event (hypertension) with the effect of apatinib on survival [ Time Frame: 2 years ]
  10. Correlation of adverse event (hand-foot syndrome) with the effect of apatinib on survival [ Time Frame: 2 years ]
  11. Correlation of the change from baseline in serum VEGF level at 4 weeks with the effect of apatinib on survival [ Time Frame: 2 years ]
  12. 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 ]


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT02874651


Contacts
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Contact: Jun Ma, M.D. +86-20-87343469 majun2@mail.sysu.edu.cn

Locations
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China, Guangdong
Affiliated Foshan Hospital of Sun Yat-sen University Not yet recruiting
Foshan, Guangdong, China, 528000
Contact: Ning Zhang, M.D.       zning@fsyyy.com   
Sun Yat-sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Jun Ma, M.D.    86-20-87343469    majun2@mail.sysu.edu.cn   
China, Guangxi
Affiliated Hospital of Guilin Medical University Not yet recruiting
Guilin, Guangxi, China, 541000
Contact: Wei Jiang, M.D.       354259301@qq.com   
Sponsors and Collaborators
Sun Yat-sen University
First People's Hospital of Foshan
Guilin Medical University, China
Investigators
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Study Chair: Jun Ma, M.D. Sun Yat-sen University

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Responsible Party: Jun Ma, MD, Prof., Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT02874651     History of Changes
Other Study ID Numbers: Ahead-N301
First Posted: August 22, 2016    Key Record Dates
Last Update Posted: November 1, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Jun Ma, MD, Sun Yat-sen University:
Nasopharyngeal Carcinoma
EB Virus
DNA
vascular endothecial growth factor receptor inhibitor
Apatinib
Additional relevant MeSH terms:
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Carcinoma
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Apatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action