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

February 9, 2015 updated by: National Health Research Institutes, Taiwan

Phase III Randomized Trial of Immediate Adjuvant Chemotherapy or Delayed Salvage Chemotherapy in Nasopharyngeal Carcinoma Patients With Post-radiation Detectable Plasma EBV DNA

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

147

Phase

  • Phase 3

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

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 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
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Adjuvant Chemotherapy
MEP followed by oral Tegafur-uracil
Drug: MEP
Adjuvant Chemotherapy
Other Names:
  • cisplatin
  • epirubicin
  • oral Tegafur-uracil
  • mitomycin-C
NO_INTERVENTION: control arm
closely followed with frequency similar to the experiemental arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to progression
Time Frame: 5 years
5 years

Secondary Outcome Measures

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

Collaborators and Investigators

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

Sponsor

National Health Research Institutes, Taiwan

Collaborators

National Taiwan University Hospital
Mackay Memorial Hospital
China Medical University Hospital
National Cheng-Kung University Hospital
Taichung Veterans General Hospital
Kaohsiung Veterans General Hospital.

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

November 1, 2014

Primary Completion (ANTICIPATED)

December 1, 2019

Study Completion (ANTICIPATED)

December 1, 2022

Study Registration Dates

First Submitted

December 4, 2014

First Submitted That Met QC Criteria

February 9, 2015

First Posted (ESTIMATE)

February 16, 2015

Study Record Updates

Last Update Posted (ESTIMATE)

February 16, 2015

Last Update Submitted That Met QC Criteria

February 9, 2015

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • T1313

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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