Proton Radiotherapy With Chemotherapy for Nasopharyngeal Carcinoma

Study Overview
=================
Brief Summary
-----------------
Photon beam radiation is the standard type of radiation used to treat nasopharyngeal carcinoma. Photon beam radiation enters the body and passes through healthy tissue, encounters the tumor and leaves the body through healthy tissue. Proton beam radiation has been shown to have the same effect on tumors as photon beam radiation but it enters the body, passes through healthy tissue, and encounters the tumor but then stops. This means less healthy tissue is affected by proton beam treatment than by photon beam treatment. The purpose of this study is to determine the effectiveness of proton beam radiation in treating nasopharyngeal cancer and reducing the acute and long-term side effects from the treatment. This study will also test to see if the sparing of the healthy tissue can improve quality of life

Detailed Description
-----------------
Before beginning study treatment, participants will be asked to fill out a Quality of Life (QOL) questionnaires, a Speech Assessment, a ChemoSensory Questionnaire, a Patient Swallowing Diary, A Swallowing Study, Salivary Tests and a Trismus Assessment. Participants will need to go to the Massachusetts Eye and Ear Infirmary (MEEI) or Massachusetts General Hospital (MGH) for these tests. Radiation therapy will be given once a day, five days a week, for seven weeks. This will be given as outpatient care at the Northeast Proton Therapy Center (proton component) and Massachusetts General Hospital (photon component). During radiation treatments, participants will receive cisplatin intravenously once every three weeks. This three-week period is called a cycle of treatment. After the completion of radiation, participants will receive cisplatin intravenously once every 4 weeks along with fluorouracil as a continuous infusion over 4 days starting on the day cisplatin is given, for three cycles. Participants will have a physical exam and blood work drawn weekly to monitor their health. An MR/CT scan of the head and neck will be done 2 months after the radiation treatment. Follow-up visits will occur once every three months for 2 years, then once every 6 months during years 3-5, then annually. During these follow-up visits, participants will have the following tests and procedures: physical examination; blood work; chest CT scan and CT/MRI of the head and neck will be repeated once every 6 months during the first three years; swallow study; salivary study; QOL questionnaires; speech assessment; ChemoSensory Questionnaire; and Trismus Assessment.

Official Title
-----------------
A Phase II Study of Proton Radiotherapy With Chemotherapy for Nasopharyngeal Carcinoma

Conditions
-----------------
Nasopharyngeal Carcinoma

Intervention / Treatment
-----------------
* Radiation: Proton/Photon Radiotherapy
* Drug: Cisplatin
* Drug: Fluorouracil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Biopsy proven greater than or equal to T2b and/or node positive non-metastatic, squamous cell carcinoma of the nasopharynx, types WHO I-III. No head and neck surgery of the primary tumor or lymph nodes except incisional or excisional biopsies. Zubrod performance status 0-1 or Karnofsky 70 or above. All patients must undergo pre-treatment evaluation of tumor extent and tumor measurement. Nutritional and general physical condition must be considered compatible with the proposed chemoradiation treatment Patients must have adequate platelet and renal function as outlined in protocol. 18 years of age or above. No active alcohol addiction. Women of childbearing potential must have a negative pregnancy test. Exclusion Criteria: Stage IVC or evidence of distant metastases Previous irradiation for head and neck tumor Patient is on other experimental therapeutic cancer treatment Other malignancy except non-melanoma skin cancer or carcinomas of head and neck origin and have been controlled for at least 5 years. Active untreated infection Major medical or psychiatric illness Prophylactic use of amifostine or pilocarpine Pregnant or breast feeding women Symptomatic peripheral neuropathy of grade 2 or greater by NCI CTCAE Symptomatic altered hearing > grade 2 by CTCAE

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proton/Photon Radiotherapy, Cisplatin, Fluorouracil<br> | Radiation: Proton/Photon Radiotherapy<br>* Given once a day, five days a week, for seven weeks.<br>Drug: Cisplatin<br>* Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles.<br>Drug: Fluorouracil<br>* Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.<br>* Other names: 5-FU;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Acute Toxicity | Acute toxicities are side affects that occur during treatment and 90 days after completion. | 54 days of chemoradiation treatment and 90 days after completion, up to 144 days total | 
| Participant Compliance Rate to Assigned Treatment Intervention |  | 2 years | 
| Sialometry to Evaluate Xerostomia (Dry Mouth) | Sialometry is a measure of saliva flow. The normal daily production of saliva varies between 0.5 and 1.5 liters. Stimulated saliva is produced in response to a mechanical, gustatory, olfactory, or pharmacological stimulus, contributing to around 40-50% of daily salivary production. In adults, normal total stimulated salivary flow ranges 1-3 mL/minute, low ranges 0.7-1.0 mL/minute, while hyposalivation is characterized by a stimulated salivary flow <0.7mL/minute. | Baseline and 2 years (24 months) | 
| Penetration-aspiration Scale to Evaluate Swallowing Function | The videofluoroscopic swallow study (VFSS) is the gold standard diagnostic tool to evaluate oropharyngeal dysphagia. The penetration-aspiration scale (PAS) is an 8-point scale used to grade the severity of penetration or aspiration observed in a videofluoroscopic swallow study. Aspiration is defined as the passing of the bolus below the true vocal folds, and penetration is when the bolus enters the airway but not below the true vocal folds. 1 is normal, no penetration or aspiration. 2-5 is penetration. 6-8 is aspiration. | Baseline and 12 months | 
| Serial Measurements of Maximal Inter-incisal Distance to Evaluate Trismus (Lockjaw) | Serial measures of the changes of the maximal inter-incisal distance in the vertical opening, right lateral, and left lateral jaw movements are used to evaluate trismus (lockjaw). An average measurement of the three directional areas will be reported. | Baseline and 2 years | 
| ChemoSensory Questionnaire (CSQ) to Evaluate Smell and Taste Function | The Chemosensory Questionnaire (CSQ) has four questions each on smell and taste. A minimum score of 4 and a maximum of 20 for the smell scale and taste scale are possible with a higher score indicating better function. | 2 years | 
| Number of Participants With Speech Problems Assessed by Head and Neck Health Status Assessment Inventory (HNHSAI) | The Head and Neck Health Status Assessment Inventory (HNHSAI) is a descriptive outcome assessment consisting of 14 yes/no questions to measure number of participants with speech problems. | 2 years | 
| Health Related Quality-of-Life Outcomes Using Validated Quality-of-Life Instrument EORTC QLQ-C30 | General quality of life is measured with the European organization for research and treatment of cancer (EORTC) quality of life questionnaire (QLQ) EORTC QLQ-C30 (cancer 30). They are self-administered questionnaires. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for the global health status / QoL represents a high QoL. | 2 years | 
| Health Related Quality-of-life Outcomes Using Validated Quality-of-life Instrument EORTC-QLQ-H&N | General quality of life is measured with the European organization for research and treatment of cancer (EORTC) quality of life questionnaires (QLQ) for head and neck (H&N) (EORTC-QLQ-H&N). The head & neck cancer module incorporates seven multi-item scales that assess pain, swallowing, senses (taste and smell), speech, social eating, social contact, and sexuality. There are also eleven single items. All of the scales and single-item measures range in score from 0 to 100. For all items and symptom scales, high scores represent a high level of symptomatology/problems. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate and Pattern of Locoregional Tumor Recurrence |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
proton radiation, photon radiation, 5-FU, cisplatin