Clinical trial NCT02460887: The Role of Induction Gemcitabine and Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma in the Era of IMRT
Official title: A Randomized Trial Comparing Induction Gemcitabine and Cisplatin Plus Intensity-modulated Radiotherapy with Concurrent Cisplatin Plus Intensity-modulated Radiotherapy in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Keywords: nasopharyngeal carcinoma
induction chemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2015-06-03
Enrollment: 236
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to verify that induction gemcitabine and cisplatin plus intensity-modulated radiotherapy (IMRT) is non-inferior to concurrent weekly cisplatin plus IMRT for patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

Detailed description: Patients with non-keratinizing NPC T1-4N2-3或T3-4N0-1M0 (UICC/AJCC 7th edition) are randomly assigned to receive induction chemotherapy or CCRT alone. Patients in experimental group receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before intensity-modulated radiotherapy (IMRT). Patients in control group receive IMRT concurrently with weekly cisplatin 40 mg/m² up to 7cycles.

IMRT is given as 2.0-2.33 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor.

Our primary endpoint is failure-free survival (FFS). Secondary end points include overall survival (OS), locoregional failure-free survival (LR-FFS), distant failure-free survival (D-FFS) rates and toxic effects. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

Eligibility criteria: Inclusion Criteria:

* Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma (including WHO II or III).
* Tumor staged as T1-4N2-3或T3-4N0-1M0 (according to the 7th AJCC edition).
* Satisfactory performance status: Karnofsky scale (KPS) ≥ 70.
* Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 90g/L and platelet count ≥ 100000/μL.
* Adequate liver function: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) \< 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤1.5×ULN.
* Adequate renal function: creatinine clearance ≥ 60 ml/min.
* Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

* WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
* Treatment with palliative intent.
* Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
* Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).
* History of previous RT (except for non-melanomatous skin cancers outside intended RT treatment volume).
* Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
* Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose \> 1.5×ULN), and emotional disturbance.

Primary outcomes:
measure: Failure-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years
measure: Locoregional failure-free survival
timeFrame: 2 years
measure: Distant failure-free survival
timeFrame: 2 years
measure: Overall response rate
timeFrame: 3 months after completion of IMRT
measure: Number of participants with adverse events
timeFrame: 2 years
measure: Quality of life during treatment
timeFrame: During whole chemotherapy and IMRT treatment.For experimental arm, an expected average of 12 weeks; for active comparator arm, an expected average of 6 weeks.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Pei-Yu Huang, M. D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
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