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

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

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma; Nasopharyngeal Neoplasms
• Intervention / Treatment: Drug: docetaxel; Drug: cisplatin; Drug: 5-fluorouracil

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• Algeria
  • Alger, Algeria, 16005
    • Investigational Site Number 012001
• Brazil
  • Rio De Janeiro, Brazil, 20230-130
    • Investigational Site Number 076002
  • Sao Paulo, Brazil, 04023-062
    • Investigational Site Number 076001
• China
  • Fuzhou, China, 350014
    • Investigational Site Number 156005
• France
  • Villejuif Cedex, France, 94805
    • Investigational Site Number 250001
• India
  • Ahmedabad, India, 380006
    • Investigational Site Number 356003
  • Kolkata, India, 700054
    • Investigational Site Number 356004
  • Thiruvananthapuram, India, 695011
    • Investigational Site Number 356002
  • Vellore, India, 632004
    • Investigational Site Number 356001
• Indonesia
  • Jakarta, Indonesia, 10430
    • Investigational Site Number 360001
• Italy
  • Milano, Italy, 20133
    • Investigational Site Number 380001
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Investigational Site Number 410003
  • Seoul, Korea, Republic of, 138-736
    • Investigational Site Number 410002
  • Seoul, Korea, Republic of, 110-744
    • Investigational Site Number 410001
• Mexico
  • Villahermosa, Mexico, 86100
    • Investigational Site Number 484001
• Morocco
  • Casablanca, Morocco, 20000
    • Investigational Site Number 504001
  • Rabat, Morocco, 10000
    • Investigational Site Number 504002
  • Rabat, Morocco
    • Investigational Site Number 504003
• Philippines
  • Quezon City, Philippines
    • Investigational Site Number 608002
• Thailand
  • Bangkok, Thailand, 10330
    • Investigational Site Number 764001
  • Chiang Mai, Thailand, 50200
    • Investigational Site Number 764002
• Tunisia
  • Sousse, Tunisia, 4000
    • Investigational Site Number 788002
  • Tunis, Tunisia, 1006
    • Investigational Site Number 788003
• Turkey
  • Abacioglu, Turkey, 34662
    • Investigational Site Number 792003
  • Ankara, Turkey, 06100
    • Investigational Site Number 792001
  • Istanbul, Turkey, 34303
    • Investigational Site Number 792002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Docetaxel/Cisplatin/5-FU (TCF); 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; Pharmaceutical form:solution for infusion Route of administration:intravenous; Other Names: Taxotere®; XRP6976; Drug: cisplatin; Pharmaceutical form:solution for infusion Route of administration:intravenous; Drug: 5-fluorouracil; Pharmaceutical form:solution for infusion Route of administration:intravenous; Other Names: 5-FU
Active Comparator: Cisplatin/5-FU (CF); 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; Pharmaceutical form:solution for infusion Route of administration:intravenous; Drug: 5-fluorouracil; Pharmaceutical form:solution for infusion Route of administration:intravenous; Other Names: 5-FU

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: November 29, 2007
• First Submitted That Met QC Criteria: November 29, 2007
• First Posted (Estimate): November 30, 2007

Study Record Updates

• Last Update Posted (Estimate): July 30, 2015
• Last Update Submitted That Met QC Criteria: July 2, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Nasopharyngeal carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Fluorouracil
• Other Study ID Numbers: EFC10339; 2007-001211-33 (EudraCT Number)