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

Phase 3

• Conditions: Nasopharyngeal Carcinoma
• Interventions: Drug: MEP

• Registration Number: NCT02363400
• Lead Sponsor: National Health Research Institutes, Taiwan

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.

Study Timeline

• Status Verified: 2014-11
• Study Start: 2014-11
• Study First Submitted: 2014-12-04
• Study First Submitted QC: 2015-02-09
• Last Update Submitted: 2015-02-09
• Study First Posted: 2015-02-16
• Last Update Posted: 2015-02-16
• Primary Completion: 2019-12
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 147

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adjuvant Chemotherapy	MEP	MEP followed by oral Tegafur-uracil

Primary Outcome Measures

Name	Time	Method
Time to progression	5 years

Secondary Outcome Measures

Name	Time	Method
Progression-free survival and relapse rate	5 years
Overall survival	5 years
Toxicity profile and tolerance, according to CTCAE 4.1	5 years
Predicting value of plasma EBV DNA	5 years