A Phase III Trial in NPC With Post-radiation Detectable Plasma EBV DNA

NCT ID: NCT02363400

Last Updated: 2025-08-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-14
• Study Completion Date: 2021-12-31

Brief Summary

Nasopharyngeal carcinoma (NPC) is a geographically endemic, Epstein-Barr virus (EBV)-associated carcinoma of epidermoid origin. It occurs most commonly in Southern China and Southeast Asia. The NPC cells are poorly differentiated or undifferentiated with a high incidence of lymphatic and hematological dissemination. Because of the inherent anatomic constraints and a high degree of radiosensitivity, radiotherapy (RT) has been the primary treatment for NPC patients.

NPC is also a chemosensitive tumor. Various modes of combined chemoradiotherapy have been used to treat NPC patients with advanced-stage diseases during recent 20 years. However, treatment outcome for locoregionally advanced NPC is still unsatisfactory.

Detailed Description

The current NCCN guidelines recommend that CCRT + adjuvant chemotherapy for advanced (stage III-IV) NPC, originated from the results of the Intergroup study [69]. However, all meta-analysis reported no any benefit in using adjuvant chemotherapy for NPC patients [82-85]. These contradictions puzzle most oncologists for decades. In our opinion, routine delivery of post-radiation adjuvant chemotherapy after RT±induction/concurrent chemotherapy for "all" advanced-stage NPC patients should be re-considered. The major goal of adjuvant chemotherapy in NPC is to reduce the occurrences of distant failure. But, not all advanced NPC patients need adjuvant chemotherapy. In our previous phase III study, only 19.1% (27/141) NPC patients with 1988 AJCC stage III-IV disease developed distant failure after CCRT . In another study of 210 NPC patients with 1997 AJCC stage IIB-IVB treated by induction chemotherapy + RT, 55 patients (26.2%) suffered from subsequent distant metastasis [67]. We should remember that unnecessary adjuvant therapy is frequently used. For example, if the target patients have as high as 50% subsequent distant failure rate, and the adjuvant therapy protocol has a 50% control rate for the subclinical disease. When we treat all target patients, only 25% patients benefit from the adjuvant therapy because of unnecessary treatment in 50% and ineffective treatment in another 25% patients. Thus, adjuvant therapy should be designed for "selected" patients. For NPC patients, pEBV DNA-guided adjuvant therapy trial is very reasonable. We plan to prove that adjuvant chemotherapy is beneficial for post-radiation detectable pEBV DNA patients in this prospective multi-center trial. We will conduct another trial to investigate (compare) which adjuvant chemotherapy regimen is the best one in the future.

Conditions

Nasopharyngeal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Adjuvant Chemotherapy

MEP followed by oral Tegafur-uracil

Group Type: EXPERIMENTAL

MEP

Intervention Type: DRUG

Adjuvant Chemotherapy

control arm

closely followed with frequency similar to the experiemental arm

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

MEP

Adjuvant Chemotherapy

Intervention Type: DRUG

Other Intervention Names

epirubicin; cisplatin; oral Tegafur-uracil; mitomycin-C

Eligibility Criteria

Inclusion Criteria

1.Histological proven NPC.

2.2010 AJCC stage II-IVB.

3.Age ≧ 20 years old.

4.Performance status of ECOG ≦ 2.

5.Finished RT ≧ 66 Gy (± induction and/or concurrent chemotherapy).

6.pEBV DNA > 0 copy/ml at 1±1 week post-RT.

7.Re-staging work-ups at 10±2 weeks post-RT showing no active lesions.

8.Adequate liver, renal, and bone marrow function 4 weeks before randomization.

9.Signed informed consent.

Exclusion Criteria

1. Pathologically-proven the presence of locoregional disease and/or distant metastasis.

2. Unequivocally-shown active NPC (locoregional/distant) by imaging studies.

3. Inadequate RT.

4. Received any post-RT adjuvant chemotherapy.

5. pEBV DNA = 0 copy/ml at 1±1 week post-RT.

6. Previous delivery of cisplatin dose > 600 mg/m2.

7. Previous delivery of epirubicin > 360 mg/m2.

8. History of a malignancy except those treated with curative intent for skin cancer (other than melanoma), in situ cervical cancer, ductal carcinoma in situ (DCIS) of breast.

9. Severe cardiopulmonary diseases (unstable angina and/or congestive heart failure or peripheral vascular disease requiring hospitalization within the last 12 months; chronic obstructive pulmonary disease exacerbation other respiratory illness requiring hospitalization) or clinically significant psychiatric disorders.

10. Female patients who are pregnant or lactating.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Health Research Institutes, Taiwan

OTHER

Sponsor Role: lead

Mackay Memorial Hospital

OTHER

Sponsor Role: collaborator

China Medical University Hospital

OTHER

Sponsor Role: collaborator

National Cheng-Kung University Hospital

OTHER

Sponsor Role: collaborator

Kaohsiung Veterans General Hospital.

OTHER

Sponsor Role: collaborator

Taichung Veterans General Hospital

OTHER

Sponsor Role: collaborator

Koo Foundation Sun Yat-Sen Cancer Center

OTHER

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jin-Ching Lin, MD, PHD

Role: STUDY_CHAIR

Taichung Veterans General Hospital

Tsang-Wu Liu, MD

Role: STUDY_DIRECTOR

National Health Research Institutes, Taiwan

Jin-Ching Lin, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Taichung Veterans General Hospital

Yi-Fang Chang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Mackay Memorial Hospital

Ching-Yun Hsieh, MD

Role: PRINCIPAL_INVESTIGATOR

China Medical University Hospital

Chia-Jui Yen Yen, MD. PhD

Role: PRINCIPAL_INVESTIGATOR

National Cheng-Kung University Hospital

Yaoh-Shiang Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Kaohsiung Veterans General Hospital.

Stella Yu-Chen Tsai, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Hsiao-Hui Tsou, PhD

Role: PRINCIPAL_INVESTIGATOR

National Health Research Institutes, Taiwan

Locations

Kaohsiung Veterans General Hospital.

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng-Kung University Hospital

Tainan City, , Taiwan

Mackay Memorial Hospital

Taipei, , Taiwan

Sun Yat-sen University

Taipei, , Taiwan

Countries

Taiwan

Other Identifiers

T1313

Identifier Type: -

Identifier Source: org_study_id