Docetaxel in Combination With Cisplatin-5-fluorouracil for the Induction Treatment of Nasopharyngeal Carcinoma in Children and Adolescents

Study Overview
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Brief Summary
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The primary objective is to estimate the Complete Response rate of docetaxel to the combination of cisplatin-5-fluorouracil (TCF) compared to cisplatin-5-fluorouracil (CF) in the Induction treatment of Nasopharyngeal Carcinoma (NPC). The secondary objectives are to determine: the safety of TCF in comparison to CF after induction treatment of NPC, the pharmacokinetics of docetaxel when added to CF, the Overall Response rate of TCF and CF on completion of induction and consolidation (chemo-radiotherapy) treatment of NPC, and to compare overall survival between TCF and CF.

Detailed Description
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Planned treatment duration: induction period: 9 weeks of induction treatment consolidation period: 9 weeks of chemoradiation treatment. The consolidation treatment was the same for all participants: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks.

Official Title
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International Randomized Study to Evaluate the Addition of Docetaxel to the Combination of Cisplatin-5-fluorouracil (TCF) vs. Cisplatin-5-fluorouracil (CF) in the Induction Treatment of Nasopharyngeal Carcinoma (NPC) in Children and Adolescents

Conditions
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Nasopharyngeal Neoplasms, Carcinoma

Intervention / Treatment
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* Drug: docetaxel
* Drug: cisplatin
* Drug: 5-fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis of nasopharyngeal carcinoma World Health Organization (WHO) type II or III Children and adolescents newly diagnosed with Stage IIB-IV NPC with measurable disease, who are >1 month to ≤21 years of age at the time of diagnosis. In France, participants must be ≥1 year to ≤21 years of age at the time of diagnosis Exclusion Criteria: Participants with short life expectancy Prior chemotherapy or radiotherapy to the nasopharynx or neck for the treatment of nasopharyngeal carcinoma Inadequate renal function evidenced by unacceptable laboratory results The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel/Cisplatin/5-FU (TCF)<br>Docetaxel 75 milligrams per square meter (mg/m²) over 1 hour on Day 1 every 3 weeks Cisplatin 75 mg/m² Day 1 over 6 hours every 3 weeks 5-Fluorouracil 750 mg/m²/day continuous infusion Days 1 to 4 every 3 weeks as an induction therapy Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks. | Drug: docetaxel<br>* Pharmaceutical form:solution for infusion Route of administration:intravenous<br>* Other names: XRP6976;Drug: cisplatin<br>* Pharmaceutical form:solution for infusion Route of administration:intravenous<br>Drug: 5-fluorouracil<br>* Pharmaceutical form:solution for infusion Route of administration:intravenous<br>* Other names: 5-FU;|
| Active Comparator: Cisplatin/5-FU (CF)<br>Cisplatin 80 mg/m² Day 1 over 6 hours every 3 weeks 5-Fluorouracil 1000 mg/m²/day continuous infusion Day 1 to 4 every 3 weeks as an induction therapy. Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks. | Drug: cisplatin<br>* Pharmaceutical form:solution for infusion Route of administration:intravenous<br>Drug: 5-fluorouracil<br>* Pharmaceutical form:solution for infusion Route of administration:intravenous<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Response (CR) | CR assessed by independent reviewers, according to the Modified Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the induction treatment and prior to the radiation treatment. CR defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) only. | after the completion of the induction treatment (up to 9 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Docetaxel Area Under the Plasma Concentration-time Curve (AUC) in the Docetaxel/Cisplatin/5-FU Group | AUC estimated by Bayesian method using concentration-time data for each participant and the previously defined adult population model as prior information (with validity of the estimation verified). | Three plasma samples: one just before then 45 minutes and 5hour after the end of cycle 1 infusion | 
| Overall Response (OR) | OR is classified as CR, partial response (PR), stable disease (SD), progressive disease (PD) or Unknown on completion of both induction and radiation treatment and assessed according to the Modified RECIST from the NCI. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as ≥30% decrease in the sum of the longest diameters (LD) of TLs, taking as reference the disease measurement done at study entry. PD is defined as ≥20% increase in the sum of the LD of TLs, taking as a reference the smallest disease measurement recorded at study entry or the appearance of ≥1 new lesions or unequivocal progression of non-TLs. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | after the completion of the consolidation treatment (up to 18 weeks) | 
| Overall Survival (OS) Rate | OS rate is the percentage of participants who survived 3 years after completion of consolidation treatment period. The Kaplan-Meier method was used to estimate OS rate. | 3 years after the end of the consolidation treatment period (up to 40 months from randomization) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma