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

Phase 2

Completed

• Conditions: Nasopharyngeal Neoplasms; Carcinoma
• Interventions: Drug: docetaxel; Drug: cisplatin; Drug: 5-fluorouracil

• Registration Number: NCT00565448
• Lead Sponsor: Sanofi

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2007-11
• Study First Submitted: 2007-11-29
• Study First Submitted QC: 2007-11-29
• Study First Posted: 2007-11-30
• Primary Completion: 2009-03
• Results First Submitted: 2010-03-05
• Results First Submitted QC: 2010-03-05
• Results First Posted: 2010-03-25
• Study Completion: 2012-01
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-02
• Last Update Posted: 2015-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Docetaxel/Cisplatin/5-FU (TCF)	cisplatin	* 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.
Docetaxel/Cisplatin/5-FU (TCF)	docetaxel	* 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.
Docetaxel/Cisplatin/5-FU (TCF)	5-fluorouracil	* 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.
Cisplatin/5-FU (CF)	cisplatin	* 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.
Cisplatin/5-FU (CF)	5-fluorouracil	* 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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Complete Response (CR)	after the completion of the induction treatment (up to 9 weeks)	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.

Secondary Outcome Measures

Name	Time	Method
Docetaxel Area Under the Plasma Concentration-time Curve (AUC) in the Docetaxel/Cisplatin/5-FU Group	Three plasma samples: one just before then 45 minutes and 5hour after the end of cycle 1 infusion	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).
Overall Response (OR)	after the completion of the consolidation treatment (up to 18 weeks)	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.
Overall Survival (OS) Rate	3 years after the end of the consolidation treatment period (up to 40 months from randomization)	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.

Trial Locations

Locations (26)

Investigational Site Number 504003; 🇲🇦 Rabat, Morocco

Investigational Site Number 608002; 🇵🇭 Quezon City, Philippines

Investigational Site Number 076002; 🇧🇷 Rio De Janeiro, Brazil

Investigational Site Number 012001; 🇩🇿 Alger, Algeria

Investigational Site Number 076001; 🇧🇷 Sao Paulo, Brazil

Investigational Site Number 156005; 🇨🇳 Fuzhou, China

Investigational Site Number 250001; 🇫🇷 Villejuif Cedex, France

Investigational Site Number 356003; 🇮🇳 Ahmedabad, India

Investigational Site Number 356004; 🇮🇳 Kolkata, India

Investigational Site Number 356002; 🇮🇳 Thiruvananthapuram, India

Investigational Site Number 410001; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 380001; 🇮🇹 Milano, Italy

Investigational Site Number 360001; 🇮🇩 Jakarta, Indonesia

Investigational Site Number 356001; 🇮🇳 Vellore, India

Investigational Site Number 410002; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 484001; 🇲🇽 Villahermosa, Mexico

Investigational Site Number 410003; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 504001; 🇲🇦 Casablanca, Morocco

Investigational Site Number 504002; 🇲🇦 Rabat, Morocco

Investigational Site Number 764001; 🇹🇭 Bangkok, Thailand

Investigational Site Number 764002; 🇹🇭 Chiang Mai, Thailand

Investigational Site Number 788003; 🇹🇳 Tunis, Tunisia

Investigational Site Number 788002; 🇹🇳 Sousse, Tunisia

Investigational Site Number 792003; 🇹🇷 Abacioglu, Turkey

Investigational Site Number 792001; 🇹🇷 Ankara, Turkey

Investigational Site Number 792002; 🇹🇷 Istanbul, Turkey