Clinical trial NCT03503136: Nedaplatin Versus Cisplatin and Capecitabine Versus Fluorouracil in IC + CCRT for Locoregionally Advanced NPC
Official title: Nedaplatin Versus Cisplatin and Capecitabine Versus Fluorouracil in Induction Chemotherapy Plus Concurrent Chemoradiotherapy for Locoregionally Advanced NPC： a Phase 3, Multicentre, Non-inferiority, Randomised Factorial Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Keywords: Nasopharyngeal Carcinoma
Induction chemotherapy
Concurrent chemoradiotherapy
Nedaplatin
Capecitabine
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Tongji Hospital
name: Wuhan Union Hospital, China
name: Peking University
name: Air Force Military Medical University, China
name: Second Affiliated Hospital of Soochow University
name: The First Affiliated Hospital of Guangdong Pharmaceutical University
name: First People's Hospital of Foshan
name: Fifth Affiliated Hospital, Sun Yat-Sen University
name: Cancer Hospital of Guizhou Province
name: Xiangya Hospital of Central South University
name: Jilin Provincial Tumor Hospital
name: Henan Cancer Hospital
name: Hunan Cancer Hospital
name: Cancer Hospital of Guangxi Medical University
name: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
name: Zhejiang Cancer Hospital
First posted: 2018-04-19
Enrollment: 632
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: This is a phase 3, multicentre, non-inferiority, randomised factorial trial. The purpose of this study is to study the efficacy and safety of nedaplatin versus cisplatin, and capecitabine versus fluorouracil in induction docetaxel, cisplatin, and fluorouracil (TPF) plus concurrent chemoradiotherapy with cisplatin (P-RT) in locoregionally advanced nasopharyngeal carcinoma (NPC).

Detailed description: In this study, patients with non-keratinizing NPC and staged III-IVA (except T3-4N0) are randomly assigned to one of the four groups: Group A: TPF+P-RT; Group B: TNF+N-RT; Group C: TPX+P-RT; Group D: TNX+N-RT. In induction chemotherapy, patients will receive docetaxel(60 mg/m2 on day 1), cisplatin or nedaplatin (60 mg/m2 on day 1) and fluorouracil (600 mg/m2 on Days 1 to 5) or capecitabine (625 mg/m2 bid, on Days 1 to 14) every three weeks for three cycles before the radical radiotherapy. Concurrent cisplatin or nedaplatin (100mg/m2 on day 1) was given every three weeks for two cycles during radiotherapy. Patients are stratified according to the treatment centers and stage. The primary endpoint is progression-free survival (PFS). Secondary end points include overall survival (OS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS), toxic effects, and quality of life (QOL). 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:

* Age 18-60
* Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO) histologically type)
* Performance status of Eastern Cooperative Oncology Group (ECOG) grade 0 or 1
* Tumor staged as American Joint Committee on Cance (AJCC) III-IVA (except T3-4N0)
* Adequate marrow: leucocyte count ≥ 4×10\^9/L, hemoglobin ≥ 90g/L and platelet count ≥ 100×10\^9/L.
* Normal liver and renal function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) ≤ 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤ ULN; 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.
* 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.
* Patients who could not tolerate or allergic to capecitabine.
* Illness that would interfere with oral medication, including dysphagia, chronic diarrhea, or ileus.

Primary outcomes:
measure: Progression-free survival
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years
measure: Distant failure-free survival
timeFrame: 3 years
measure: Locoregional failure-free survival
timeFrame: 3 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (acute toxicity) and RTOG/EORTC (late toxicity)
timeFrame: Up to 3 years
measure: Quality of life (QOL) as assessed by EORTC quality of life questionnaire(QLQ)-C30
timeFrame: Up to 16 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: Principal Investigator Principal Investigator, M.D.
role: PRINCIPAL_INVESTIGATOR
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