Therapeutic Gain by Induction-concurrent Chemoradiotherapy and/or Accelerated Fractionation for Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The objectives of this clinical study are threefold: To compare the benefits in cancer control and survival obtained from adding induction-concurrent chemotherapy to radiation with those from adding concurrent-adjuvant chemotherapy to radiation. To test whether replacing fluorouracil with Xeloda in combining with cisplatin in the chemotherapy plan will maintain or improve further the chemotherapy benefits while reducing the duration of hospital stay. To see if accelerated fractionation radiotherapy can improve the outcome of patients as compared with conventional fractionation radiotherapy.

Detailed Description
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primary objectives include comparing induction chemotherapy with Cisplatin + 5-Fluorouracil versus adjuvant chemotherapy with Cisplatin + 5-Fluorouracil(PF-Pvs P-PF) comparing induction chemotherapy with Cisplatin + Capecitabine versus adjuvant chemotherapy with Cisplatin + 5-Fluorouracil(PX-P vs P-PF) comparing accelerated fractionation versus conventional fractionation (AF vs CF)radiotherapy. secondary objectives include comparing induction chemotherapy with Cisplatin + Capecitabine versus induction chemotherapy with Cisplatin + 5-Fluorouracil(PX-P vs PX-P) Comparing concurrent-adjuvant (CA) versus induction-concurrent (IC) chemotherapy sequence.

Official Title
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Randomized Trial to Evaluate Therapeutic Gain by Changing Chemoradiotherapy From Concurrent-adjuvant to Induction-concurrent Sequence, and Radiotherapy From Conventional to Accelerated Fractionation for Advanced Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Adjuvant chemotherapy using PF (5-Fluorouracil )
* Drug: Induction chemotherapy using PF (5-Fluorouracil)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically proven nasopharyngeal carcinoma for primary treatment with radical intent non-keratinizing or undifferentiated type stage III-IVB (by AJCC/UICC 6th edition) ECOG Performance status less or equal to 2 Marrow: WBC >= 4 and platelet >=100 Renal: creatinine clearance >=60 Informed consent Exclusion Criteria: Primary treatment with palliative intent WHO type I squamous cell carcinoma or adenocarcinoma Evidence of distant metastases Patient is pregnant or lactating Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer or other cancer for which the patient has been disease-free for 5 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1A<br>Concurrent-Adjuvant CRT using P-PF regimen and conventional fractionation radiotherapy | Drug: Adjuvant chemotherapy using PF (5-Fluorouracil )<br>* Cisplatin 80 mg/m2 IV + 5-Fluorouracil 1000 mg/m2/day IV infusion for 96 hr every 28 days for 3 cycles<br>|
| Experimental: 1B<br>Concurrent-Adjuvant CRT using P-PF regimen and accelerated fractionation radiotherapy | Drug: Adjuvant chemotherapy using PF (5-Fluorouracil )<br>* Cisplatin 80 mg/m2 IV + 5-Fluorouracil 1000 mg/m2/day IV infusion for 96 hr every 28 days for 3 cycles<br>|
| Experimental: 2A<br>Induction-Concurrent CRT using PF-P regimen and conventional fractionation radiotherapy | Drug: Induction chemotherapy using PF (5-Fluorouracil)<br>* Cisplatin 100 mg/m2 IV + 5-Fluorouracil 1000 mg/m2/day IV infusion for 120 hr every 21 days for 3 cycles<br>|
| Experimental: 2B<br>Induction-Concurrent CRT using PF-P regimen and accelerated fractionation radiotherapy | Drug: Induction chemotherapy using PF (5-Fluorouracil)<br>* Cisplatin 100 mg/m2 IV + 5-Fluorouracil 1000 mg/m2/day IV infusion for 120 hr every 21 days for 3 cycles<br>|
| Experimental: 3A<br>Induction-Concurrent CRT using PX-P regimen and conventional fractionation radiotherapy | Drug: Capecitabine<br>* Dose:1000 mg/m2, BD, Day 1-Day 14 Interval: 21 days Cycles: 3 cycles<br>* Other names: Xeloda;|
| Experimental: 3B<br>Induction-Concurrent CRT using PX-P regimen and accelerated fractionation radiotherapy | Drug: Capecitabine<br>* Dose:1000 mg/m2, BD, Day 1-Day 14 Interval: 21 days Cycles: 3 cycles<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival, defined as the time to treatment failure at any site or death due to any cause, at 5-year. |  | 5 years | 
| Overall Survival, defined as the time to death due to any cause, at 5-year. |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall Failure-Free Rate, defined as time to failure at any site) |  | 5 years | 
| Loco-regional Failure-Free Rate, defined as time to local or nodal failure) |  | 5 years | 
| Distant Failure-Free Rate, defined as time to distant failure) |  | 5 years | 
| Incidence of chemotherapy toxicity and acute RT toxicity grade > 3 |  | treatment | 
| Time to late toxicity (From the date of randomization to the earliest date of late toxicity grade > 3) |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal Carcinoma, Chemoradiotherapy, Accelerated Fractionation