A Phase II Clinical Trial on Comparison of Effectiveness and Safeness of Different Amifostine Regimens

Study Overview
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Brief Summary
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RATIONALE Radiotherapy is the primary therapeutic strategy for nasopharyngeal carcinoma. Radiotherapy may cause adverse effect such as xerostomia and mucositis. Amifostine has the ability of protecting the normal tissue but also has some side effects. PURPOSE This phase II trial is to study the protecting effect and safety of different Amifostine regimens in patients with nasopharyngeal carcinoma.

Detailed Description
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RATIONALE: Nasopharyngeal carcinoma is a kind of malignant tumor which is treated primarily by radiation therapy. This therapeutic strategy often causes adverse effects such as dysfunction of salivary gland and lesion of oral mucosa. With concurrent chemotherapy, it may also cause toxicity to kidney, bone marrow, and other organs or tissues. When administered prior to chemoradiotherapy, Amifostine has been proved to has the ability of protecting the normal from these adverse effects so as to improve the patient tolerance. However, there are also some side effects of Amifostine itself, such as nausea, vomiting and hypotension, especially when high dose is applied. PURPOSE: This phase II randomized controlled trial is to study the protecting effect and its safety of Amifostine every-other-day regimen compared with standard everyday regimen on adverse effects such as myelosuppression, xerostomia and mucositis, in patients with nasopharyngeal carcinoma Stage T1-T4, N0-N3, M0 and undergoing concurrent chemoradiotherapy.

Official Title
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A Multi-institutional, Randomized Parallel Controlled, Phase II Clinical Trial on Comparison of Effectiveness and Safeness of Amifostine Every-other-day Regimen and Everyday Regimen From Monday to Friday

Conditions
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Nasopharyngeal Neoplasms, Salivary Gland Diseases, Bone Marrow Diseases, Mucositis

Intervention / Treatment
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* Drug: Amifostine every-other-day regimen
* Drug: Amifostine everyday regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nasopharyngeal cancer patients diagnosed by pathology or cytology UICC/AJCC 2010 Stage T1-4 N0-3 M0 Male or female patients with age between 18 and 75 years old Karnofsky Performance Scores ≥ 60 Expected survival ≥ 3 months Without dysfunction of heart, lung, liver, kidney and hematopoiesis No previous allergic reaction to the drug Exclusion Criteria: History of alcohol or drug abuse within 3 months Pregnant or lactating women Currently under treatment with other similar drugs Anti-hypertension drugs applied in less than 24 hours Severe hypocalcemia Dysfunction of heart, lung, liver, kidney or hematopoiesis Severe neurological, mental or endocrine diseases Previous allergic reaction to the drug Patients participated in clinical trials of other drugs within last 3 months Other unsuitable reason

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Program I<br>Patients with American Joint Cancer Committee/Union Internationale Contre le Cancer (UICC/AJCC) 2010 Stage I and II; Radiotherapy applied | |
| Experimental: Program II<br>Patients with UICC/AJCC 2010 Stage I and II; Radiotherapy applied; Amifostine every-other-day regimen | Drug: Amifostine every-other-day regimen<br>* Amifostine 400mg/d, every-other-day regimen from Monday to Friday, every week repetition during radiotherapy<br>* Other names: Amifostine administered 3 times per week regimen;|
| Active Comparator: Program III<br>Patients with UICC/AJCC 2010 Stage I and II; Radiotherapy applied; Amifostine everyday regimen | Drug: Amifostine everyday regimen<br>* Amifostine 400mg/d, everyday regimen from Monday to Friday, every week repetition during radiotherapy<br>* Other names: Amifostine administered 5 times per week regimen;|
| No Intervention: Program IV<br>Patients with UICC/AJCC 2010 Stage III, IVa and IVb; Concurrent chemoradiotherapy applied | |
| Experimental: Program V<br>Patients with UICC/AJCC 2010 Stage III, IVa and IVb; Concurrent chemoradiotherapy applied; Amifostine every-other-day regimen | Drug: Amifostine every-other-day regimen<br>* Amifostine 400mg/d, every-other-day regimen from Monday to Friday, every week repetition during radiotherapy<br>* Other names: Amifostine administered 3 times per week regimen;|
| Active Comparator: Program VI<br>Patients with UICC/AJCC 2010 Stage III, IVa and IVb; Concurrent chemoradiotherapy applied; Amifostine everyday regimen | Drug: Amifostine everyday regimen<br>* Amifostine 400mg/d, everyday regimen from Monday to Friday, every week repetition during radiotherapy<br>* Other names: Amifostine administered 5 times per week regimen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on improving myelosuppression | Severity of myelosuppression is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria. | One week before radiotherapy; Once a week during radiotherapy, up to 7 weeks; Three months after radiotherapy | 
| Effect on improving xerostomia | Severity of xerostomia is evaluated on basis of CTCAE 4.0 criteria. | One week before radiotherapy; Once a week during radiotherapy, up to 7 weeks; Three months after radiotherapy | 
| Effect on improving mucositis | Severity of mucositis is evaluated on basis of CTCAE 4.0 criteria. | One week before radiotherapy; Once a week during radiotherapy, up to 7 weeks; Three months after radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on improving Quality of Life (QOL). |  | One week before radiotherapy; Once a week during radiotherapy, up to 7 weeks; Three months after radiotherapy | 
| Effect on improving Karnofsky Performance Scores (KPS) |  | One week before radiotherapy; Once a week during radiotherapy, up to 7 weeks; Three months after radiotherapy | 
| Incidence and severity of Nausea | One of the adverse effects of Amifostine. | One week before radiotherapy; Once a week during radiotherapy, up to 7 weeks; Three months after radiotherapy | 
| Incidence and severity of Vomiting | One of the adverse effects of Amifostine. | One week before radiotherapy; Once a week during radiotherapy, up to 7 weeks; Three months after radiotherapy | 
| Incidence and severity of Hypotension | One of the adverse effects of Amifostine. | One week before radiotherapy; Once a week during radiotherapy, up to 7 weeks; Three months after radiotherapy | 
| Incidence and severity of Hypocalcemia | One of the adverse effects of Amifostine. | One week before radiotherapy; Once a week during radiotherapy, up to 7 weeks; Three months after radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xerostomia, Nasopharyngeal carcinoma, Amifostine, Myelosuppression, Mucositis