Nasopharyngeal Carcinoma
Conditions
Keywords
proton radiation, photon radiation, 5-FU, cisplatin
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.
Interventions
RADIATIONProton/Photon Radiotherapy
Given once a day, five days a week, for seven weeks.
DRUGCisplatin
Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles.
DRUGFluorouracil
Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy.
Sponsors
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Health Related Quality-of-life Outcomes Using Validated Quality-of-life Instrument EORTC-QLQ-H&N | 2 years | 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. |
| Number of Participants With Acute Toxicity | 54 days of chemoradiation treatment and 90 days after completion, up to 144 days total | Acute toxicities are side affects that occur during treatment and 90 days after completion. |
| Participant Compliance Rate to Assigned Treatment Intervention | 2 years | — |
| Sialometry to Evaluate Xerostomia (Dry Mouth) | Baseline and 2 years (24 months) | 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. |
| Penetration-aspiration Scale to Evaluate Swallowing Function | Baseline and 12 months | 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. |
| Serial Measurements of Maximal Inter-incisal Distance to Evaluate Trismus (Lockjaw) | Baseline and 2 years | 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. |
| ChemoSensory Questionnaire (CSQ) to Evaluate Smell and Taste Function | 2 years | 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. |
| Number of Participants With Speech Problems Assessed by Head and Neck Health Status Assessment Inventory (HNHSAI) | 2 years | 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. |
| Health Related Quality-of-Life Outcomes Using Validated Quality-of-Life Instrument EORTC QLQ-C30 | 2 years | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Rate and Pattern of Locoregional Tumor Recurrence | 3 years |
Countries
United States
Participant flow
Recruitment details
Study period: 2006 and 2011 Location: Outpatient clinic at the Massachusetts General Hospital
Participants by arm
| Arm | Count |
|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil Proton/Photon Radiotherapy: Given once a day, five days a week, for seven weeks.
Cisplatin: Given intravenously once every three weeks during radiation treatment, then once every four weeks for three cycles.
Fluorouracil: Given as continuous infusion over 4 days starting on the day cisplatin is received after radiation therapy. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Participant found to have metastatic disease after enrollment thus deemed ineligible | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Proton/Photon Radiotherapy, Cisplatin, Fluorouracil |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 48 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 23 |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 1 / 23 |
Outcome results
Primary
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.
Time frame: 2 years
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | ChemoSensory Questionnaire (CSQ) to Evaluate Smell and Taste Function | Taste score post-treatment | 17 score on a scale | Standard Error 1.05 |
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | ChemoSensory Questionnaire (CSQ) to Evaluate Smell and Taste Function | Smell score post-treatment | 18 score on a scale | Standard Error 1.06 |
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Health Related Quality-of-Life Outcomes Using Validated Quality-of-Life Instrument EORTC QLQ-C30 | 83 Global Health Status score on a scale | Standard Deviation 20.9 |
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Health Related Quality-of-life Outcomes Using Validated Quality-of-life Instrument EORTC-QLQ-H&N | 11.4 dry mouth score on a scale | Standard Error 3 |
Primary
Number of Participants With Acute Toxicity
Acute toxicities are side affects that occur during treatment and 90 days after completion.
Time frame: 54 days of chemoradiation treatment and 90 days after completion, up to 144 days total
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Number of Participants With Acute Toxicity | 23 Participants |
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Number of Participants With Speech Problems Assessed by Head and Neck Health Status Assessment Inventory (HNHSAI) | 0 participants |
Primary
Participant Compliance Rate to Assigned Treatment Intervention
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Participant Compliance Rate to Assigned Treatment Intervention | Received at least 2 cycles of concurrent chemotherapy | 100 percentage of participants |
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Participant Compliance Rate to Assigned Treatment Intervention | Received at least 2 cycles of adjuvant chemotherapy | 75 percentage of participants |
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Participant Compliance Rate to Assigned Treatment Intervention | Received 3 cycles of concurrent chemotherapy | 83 percentage of participants |
Primary
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.
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Penetration-aspiration Scale to Evaluate Swallowing Function | Penetration-aspiration scale at baseline | 1.04 score on a scale |
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Penetration-aspiration Scale to Evaluate Swallowing Function | Penetration-aspiration scale at 12 months after radiation therapy | 1.36 score on a scale |
Primary
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.
Time frame: Baseline and 2 years
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Serial Measurements of Maximal Inter-incisal Distance to Evaluate Trismus (Lockjaw) | Maximal inter-incisal distance at baseline | 51.4 millimeters | Standard Deviation 5.5 |
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Serial Measurements of Maximal Inter-incisal Distance to Evaluate Trismus (Lockjaw) | Maximal inter-incisal distance at 2 years | 43.8 millimeters | Standard Deviation 6.8 |
Primary
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.
Time frame: Baseline and 2 years (24 months)
Population: The mean values below are for all analyzed participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Sialometry to Evaluate Xerostomia (Dry Mouth) | Unstimatulated saliva at baseline | 1.89 milliliters | Standard Deviation 1.16 |
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Sialometry to Evaluate Xerostomia (Dry Mouth) | Unstimulated saliva at 24 months | 0.95 milliliters | Standard Deviation 0.57 |
Secondary
Rate and Pattern of Locoregional Tumor Recurrence
Time frame: 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Rate and Pattern of Locoregional Tumor Recurrence | Local recurrence in high-dose region | 2 participants |
| Proton/Photon Radiotherapy, Cisplatin, Fluorouracil | Rate and Pattern of Locoregional Tumor Recurrence | Distant recurrence | 3 participants |