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

December 25, 2021 updated by: Jun Ma, MD, Sun Yat-sen University

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

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Foshan, Guangdong, China, 528000
        • Affiliated Foshan Hospital of Sun Yat-sen University
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-sen University Cancer Center
    • Guangxi
      • Guilin, Guangxi, China, 541000
        • Affiliated Hospital of Guilin Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Disease-free survival
Time Frame: 3 years
3 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Collaborators

Guilin Medical University, China
First People's Hospital of Foshan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2016

Primary Completion (Actual)

November 29, 2018

Study Completion (Actual)

August 27, 2020

Study Registration Dates

First Submitted

August 1, 2016

First Submitted That Met QC Criteria

August 17, 2016

First Posted (Estimate)

August 22, 2016

Study Record Updates

Last Update Posted (Actual)

January 11, 2022

Last Update Submitted That Met QC Criteria

December 25, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ahead-N301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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