Clinical trial NCT00201396: A Multicenter Trial Comparing Induction C/T Followed by CCRT v.s. CCRT Alone in Stage IV Nasopharyngeal Carcinoma
Official title: A Multicenter Phase III Trial Comparing Induction Chemotherapy Followed by Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy Alone in Stage IV Nasopharyngeal Carcinoma (NPC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Keywords: A Multicenter Phase III Trial
Induction Chemotherapy
Concurrent Chemoradiotherapy
Stage IV Nasopharyngeal Carcinoma (NPC)
randomization
disease-free survival
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital
name: Tri-Service General Hospital
name: Chang Gung Memorial Hospital
name: China Medical University Hospital
name: Chung Shan Medical University
name: Changhua Christian Hospital
name: Chi Mei Medical Hospital
name: Kaohsiung Medical University Chung-Ho Memorial Hospital
name: Kaohsiung Veterans General Hospital.
name: Taipei Veterans General Hospital, Taiwan
First posted: 2005-09-20
Enrollment: 480
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigate the effect of induction MEPFL chemotherapy followed by concurrent chemoradiotherapy (CCRT) on the disease control and survival in treatment of patients with advanced NPC.

Detailed description: Rationale of induction chemotherapy:

Distant metastasis is the major cause of treatment failure and deaths in patients with loco-regionally advanced NPC.

Concurrent chemoradiotherapy may prolong survivals for patients with advanced NPC, but it is still flawed by high incidence of distant metastasis.

Induction chemotherapy with MEPFL has been shown to reduce the incidence of distant metastasis in a Phase II study.

Induction chemotherapy plus concurrent chemoradiotherapy may improve the survival of patients with advanced NPC.

Objectives:

Investigate the effect of induction MEPFL chemotherapy followed by concurrent chemoradiotherapy (CCRT) on the disease control and survival in treatment of patients with advanced NPC.

Study design:

This is a randomized, multi-center Phase III study. Patients will be randomized to CCRT with or without the MEPFL induction chemotherapy.

Type and number of patients:

Patients with stage IVA (T4) and/or IVB (N3) but without distant metastasis will be enrolled. A total of up to 480 patients will be randomized to detect an improvement of median overall survival from 5.8 to 8.7 years, with an a=0.05 and power of 0.8 using a two-sided logrank test with one interim analysis.

Treatment schedule:

Induction chemotherapy and CCRT:

Arm A: Weekly cisplatin concurrently with radiotherapy Arm B: Induction MEPFL three cycles followed with weekly cisplatin concurrently with radiotherapy.

Study endpoints:

The primary endpoint is the disease-free survival that will be calculated as the duration between the date of randomization and the date of recurrence of NPC at any site including persistent disease after +induction chemotherapy/CCRT, or death from any cause (failed), or the date of withdrawal (last contact date, censored), or the scheduled data analysis date (censored).( revised 8/27/2004)

Eligibility criteria: Inclusion Criteria:

* Histologically proved nasopharyngeal carcinoma.
* T4NxM0 or TxN3M0 disease by UICC/AJCC 1997 staging system. (30)
* Eastern Cooperative Oncology Group performance status \< 2.
* A leukocyte count ≥3750/mL, Hb ≥ 10 g/dL, and a platelet count ≥100,000/mL.
* A serum bilirubin level \< 1.5 mg/dL, serum creatinine level \< 1.6 mg/dL or creatinine clearance \> 60 mL/min.
* Age less than 70 years old
* An informed consent signed.

Exclusion Criteria:

* Evidence of metastatic disease.
* Presence of another malignancy other than treated squamous/basal cell carcinoma of the skin.
* Presence of uncontrolled hypertension, poorly controlled heart failure.
* Presence of active infection.
* Patients who have been or are being treated with chemotherapy, radiotherapy, immunotherapy, or other experimental therapies.
* Women who test positive for pregnancy.

Primary outcomes:
measure: The primary endpoint is the disease-free survival.
timeFrame: 10 years
Secondary outcomes:
measure: Secondary endpoints include overall survival and tumor response rate.
timeFrame: 10 years
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang-Gung Memorial Hospital(Lin-Kou),
Study officials:
affiliation: Taiwan cooperative oncology group
name: Ruey-Long Hong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hong RL, Hsiao CF, Ting LL, Ko JY, Wang CW, Chang JTC, Lou PJ, Wang HM, Tsai MH, Lai SC, Liu TW. Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study. Ann Oncol. 2018 Sep 1;29(9):1972-1979. doi: 10.1093/annonc/mdy249.