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

NCT ID: NCT02874651

Last Updated: 2022-01-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2020-08-27

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.

Conditions

Nasopharyngeal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Apatinib

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

YN968D1; Placebo tablet

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First People's Hospital of Foshan

OTHER

Sponsor Role: collaborator

Guilin Medical University, China

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Jun Ma, MD

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Ma, M.D.

Role: STUDY_CHAIR

Sun Yat-sen University

Locations

Affiliated Foshan Hospital of Sun Yat-sen University

Foshan, Guangdong, China

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Affiliated Hospital of Guilin Medical University

Guilin, Guangxi, China

Countries

China

Other Identifiers

Ahead-N301

Identifier Type: -

Identifier Source: org_study_id