ADjuVant Apatinib in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy (ADVANCE)
Primary Purpose
Nasopharyngeal Neoplasms
Status
Terminated
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Apatinib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Nasopharyngeal Neoplasms focused on measuring Nasopharyngeal Carcinoma, EB Virus, DNA, vascular endothecial growth factor receptor inhibitor, Apatinib
Eligibility Criteria
Inclusion Criteria:
- Biopsy proven nasopharyngeal carcinoma, with detectable pretreatment plasma EBV DNA
- Have detectable plasma EBV DNA at the end of (+/- 1 week) curative radiotherapy or chemoradiotherapy (radiation dose > 66Gy), determined by the central lab
- No clinical evidence of persistent loco-regional disease
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Anticipated survival >= 3 months
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
- Platelets > 80,000 cells/mm^3
- Hemoglobin >= 8.0 g/dl (no transfusion within the last 14 days)
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x institutional ULN
- Creatinine clearance (CC) >= 50 ml/min estimated by Cockcroft-Gault formula
Exclusion Criteria:
- 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
- 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
- History of serious hemorrhage events or grade 3 or higher hemorrhage within 4 weeks prior to registration
- 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)
- Proteinuria
- 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
- Thrombosis within the last 1 year, except cured vein thrombosis related to vein indwelling catheter
- Unhealed bone fracture or chronic unhealed wound
- Illness that would interfere with oral medication, including dysphagia, chronic diarrhea, or ileus
- Pregnant or lactating women
- 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
- Current drug abuse or mentally disabled
- History of congenital or acquired immune deficiency disease or organ transplantation
- Major medical illness, which in the investigator's opinion would endanger the patients or interfere with the completion of therapy and follow up
Sites / Locations
- Affiliated Foshan Hospital of Sun Yat-sen University
- Sun Yat-sen University Cancer Center
- Affiliated Hospital of Guilin Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Apatinib
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Disease-free survival
Secondary Outcome Measures
overall survival
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Changes in quality of life (QOL) as assessed by EORTC QLQ-C30
Distance Metastasis Free Survival
locoregional relapse free survival
Correlation of plasma EBV DNA load with the effect of apatinib on survival
Correlation of pretreatment serum VEGF level with the effect of apatinib on survival
Correlation of pretreatment serum VEGFR-2 level with the effect of apatinib on survival
Correlation of adverse event (hypertension) with the effect of apatinib on survival
Correlation of adverse event (hand-foot syndrome) with the effect of apatinib on survival
Correlation of the change from baseline in serum VEGF level at 4 weeks with the effect of apatinib on survival
Correlation of the change from baseline in serum VEGFR-2 level at 4 weeks with the effect of apatinib on survival
Full Information
NCT ID
NCT02874651
First Posted
August 1, 2016
Last Updated
December 25, 2021
Sponsor
Sun Yat-sen University
Collaborators
First People's Hospital of Foshan, Guilin Medical University, China
1. Study Identification
Unique Protocol Identification Number
NCT02874651
Brief Title
ADjuVant Apatinib in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy
Acronym
ADVANCE
Official Title
ADjuVant Apatinib in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy With or Without Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
Unacceptable toxicity (nasopharynx necrosis and massive hemorrhage)
Study Start Date
October 2016 (undefined)
Primary Completion Date
November 29, 2018 (Actual)
Study Completion Date
August 27, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
First People's Hospital of Foshan, Guilin Medical University, China
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Neoplasms
Keywords
Nasopharyngeal Carcinoma, EB Virus, DNA, vascular endothecial growth factor receptor inhibitor, Apatinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Apatinib
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Apatinib
Other Intervention Name(s)
YN968D1
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo tablet
Intervention Description
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.
Primary Outcome Measure Information:
Title
Disease-free survival
Time Frame
3 years
Secondary Outcome Measure Information:
Title
overall survival
Time Frame
5 years
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
2 years
Title
Changes in quality of life (QOL) as assessed by EORTC QLQ-C30
Time Frame
2 years
Title
Distance Metastasis Free Survival
Time Frame
3 years
Title
locoregional relapse free survival
Time Frame
3 years
Title
Correlation of plasma EBV DNA load with the effect of apatinib on survival
Time Frame
3 years
Title
Correlation of pretreatment serum VEGF level with the effect of apatinib on survival
Time Frame
3 years
Title
Correlation of pretreatment serum VEGFR-2 level with the effect of apatinib on survival
Time Frame
3 years
Title
Correlation of adverse event (hypertension) with the effect of apatinib on survival
Time Frame
3 years
Title
Correlation of adverse event (hand-foot syndrome) with the effect of apatinib on survival
Time Frame
3 years
Title
Correlation of the change from baseline in serum VEGF level at 4 weeks with the effect of apatinib on survival
Time Frame
3 years
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Biopsy proven nasopharyngeal carcinoma, with detectable pretreatment plasma EBV DNA
Have detectable plasma EBV DNA at the end of (+/- 1 week) curative radiotherapy or chemoradiotherapy (radiation dose > 66Gy), determined by the central lab
No clinical evidence of persistent loco-regional disease
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
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Anticipated survival >= 3 months
Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
Platelets > 80,000 cells/mm^3
Hemoglobin >= 8.0 g/dl (no transfusion within the last 14 days)
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x institutional ULN
Creatinine clearance (CC) >= 50 ml/min estimated by Cockcroft-Gault formula
Exclusion Criteria:
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
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
History of serious hemorrhage events or grade 3 or higher hemorrhage within 4 weeks prior to registration
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)
Proteinuria
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
Thrombosis within the last 1 year, except cured vein thrombosis related to vein indwelling catheter
Unhealed bone fracture or chronic unhealed wound
Illness that would interfere with oral medication, including dysphagia, chronic diarrhea, or ileus
Pregnant or lactating women
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
Current drug abuse or mentally disabled
History of congenital or acquired immune deficiency disease or organ transplantation
Major medical illness, which in the investigator's opinion would endanger the patients or interfere with the completion of therapy and follow up
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Ma, M.D.
Organizational Affiliation
Sun Yat-sen University
Official's Role
Study Chair
Facility Information:
Facility Name
Affiliated Foshan Hospital of Sun Yat-sen University
City
Foshan
State/Province
Guangdong
ZIP/Postal Code
528000
Country
China
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Facility Name
Affiliated Hospital of Guilin Medical University
City
Guilin
State/Province
Guangxi
ZIP/Postal Code
541000
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
ADjuVant Apatinib in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy
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