Carcinoma, Nasopharyngeal Neoplasms
Conditions
Keywords
Nasopharyngeal carcinoma
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.
Interventions
DRUGdocetaxel
Pharmaceutical form:solution for infusion Route of administration:intravenous
DRUGcisplatin
Pharmaceutical form:solution for infusion Route of administration:intravenous
DRUG5-fluorouracil
Pharmaceutical form:solution for infusion Route of administration:intravenous
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 21 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Algeria, Brazil, China, France, India, Indonesia, Italy, Mexico, Morocco, Philippines, South Korea, Thailand, Tunisia, Turkey (Türkiye)
Participant flow
Recruitment details
Participants were enrolled from November 2007 until October 2008. The study was conducted at 26 centers in 14 countries.
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel /Cisplatin/5-FU Docetaxel 75 mg/m² in combination with Cisplatin 75 mg/m² on Day 1 and 5-Fluorouracil 750 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy.
Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks. | 50 |
| Cisplatin/5-FU Cisplatin 80 mg/m² on Day 1 and 5-Fluorouracil 1000 mg/m²/day on Days 1 to 4 every 3 weeks as induction therapy.
Consolidation treatment: radiation therapy for 7-8 weeks and 3 cycles of cisplatin 100 mg/m² every 3 weeks. | 25 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Disease progression | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Docetaxel /Cisplatin/5-FU | Cisplatin/5-FU | Total |
|---|---|---|---|
| Age, Continuous | 16 years | 16 years | 16 years |
| Age, Customized Adolescents >=16 | 26 participants | 14 participants | 40 participants |
| Age, Customized Adolescents from 12 years to <16 years | 20 participants | 10 participants | 30 participants |
| Age, Customized Children from 2 years to <12 years | 4 participants | 1 participants | 5 participants |
| Age, Customized Infants from 28 days to 23 months | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 15 Participants | 6 Participants | 21 Participants |
| Sex: Female, Male Male | 35 Participants | 19 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 25 | 49 / 50 |
| serious Total, serious adverse events | 11 / 25 | 20 / 50 |
Outcome results
Primary
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.
Time frame: after the completion of the induction treatment (up to 9 weeks)
Population: ITT population: all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel /Cisplatin/5-FU | Number of Participants With Complete Response (CR) | 1 participants |
| Cisplatin/5-FU | Number of Participants With Complete Response (CR) | 0 participants |
Comparison: There was no formal power calculation. A selection design was used to determine how many participants would be accrued to correctly select the treatment group with the best CR rate with 80% probability.p-value: 1Fisher Exact
Secondary
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).
Time frame: Three plasma samples: one just before then 45 minutes and 5hour after the end of cycle 1 infusion
Population: Participants who were randomized to docetaxel/cisplatin/5-FU and had evaluable docetaxel pharmacokinetic (PK) sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Docetaxel /Cisplatin/5-FU | Docetaxel Area Under the Plasma Concentration-time Curve (AUC) in the Docetaxel/Cisplatin/5-FU Group | 3.43 µg*h/mL | Standard Deviation 2.05 |
Secondary
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.
Time frame: after the completion of the consolidation treatment (up to 18 weeks)
Population: ITT population: all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel /Cisplatin/5-FU | Overall Response (OR) | Missing | 2 participants |
| Docetaxel /Cisplatin/5-FU | Overall Response (OR) | CR | 1 participants |
| Docetaxel /Cisplatin/5-FU | Overall Response (OR) | PR | 43 participants |
| Docetaxel /Cisplatin/5-FU | Overall Response (OR) | SD | 2 participants |
| Docetaxel /Cisplatin/5-FU | Overall Response (OR) | PD | 2 participants |
| Docetaxel /Cisplatin/5-FU | Overall Response (OR) | Unknown | 0 participants |
| Cisplatin/5-FU | Overall Response (OR) | PD | 0 participants |
| Cisplatin/5-FU | Overall Response (OR) | Missing | 3 participants |
| Cisplatin/5-FU | Overall Response (OR) | SD | 1 participants |
| Cisplatin/5-FU | Overall Response (OR) | CR | 1 participants |
| Cisplatin/5-FU | Overall Response (OR) | Unknown | 0 participants |
| Cisplatin/5-FU | Overall Response (OR) | PR | 20 participants |
Secondary
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.
Time frame: 3 years after the end of the consolidation treatment period (up to 40 months from randomization)
Population: ITT population: all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel /Cisplatin/5-FU | Overall Survival (OS) Rate | 85.7 percentage of participants |
| Cisplatin/5-FU | Overall Survival (OS) Rate | 78.0 percentage of participants |