IRB Number:

07-007844

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

Patients are being asked to take part in this research study because they have a rare malignant (cancerous) tumor called nasopharyngeal carcinoma (NPC). The tumor is in the nasopharynx, the upper part of the throat behind the nose. Air passes through it to the lungs and food passes through it as it is swallowed. An opening on each side of the nasopharynx leads into an ear.

Because of where it sits, an NPC-type tumor cannot usually be totally removed by surgery. Standard (usual) treatment for people diagnosed very early is radiation therapy only. Others, with more advanced disease get chemotherapy and radiation therapy. These people commonly have larger tumors, or cancer that has spread to the lymph nodes of the neck. This study will use radiation therapy, chemotherapy and chemoradiotherapy.
- Radiation therapy is the use of high-energy x-rays or other types of radiation to kill cancer cells.
- Chemotherapy is the use of anti-cancer drugs to stop the growth of cancer cells.
- Chemoradiotherapy is chemotherapy given at the same time as radiation therapy


Why Is This Study Being Done?
Recent studies done in adults have shown that chemoradiotherapy works better than radiation therapy followed by chemotherapy.

Studies in adults have also shown that the drug amifostine can help prevent the loss of, and thickening of, saliva. This side effect of radiation therapy to the head and neck causes dryness of the mouth which leads to dental problems, problems swallowing and infections.

The goals of this study are:
1) To see if a combination of chemotherapy followed by chemoradiotherapy works better at treating children with advanced NPC than the standard therapy.
2) To see how well amifostine protects children against dry mouth when given daily before radiation therapy.

Who is Eligible to Participate in the Study?

-Patients must be less then 19 years of age at time of diagnosis
-Diagnosed with rare malignant (cancerous) tumor called nasopharyngeal carcinoma (NPC)
-Received no previous chemotherapy or radiotherapy to the nasopharynx or neck for the treatment of nasopharyngeal carcinoma.

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

Before starting the study
Patients will need to have the following exams, tests or procedures to find out if they can be in the study. These exams, tests or procedures are part of regular cancer care and may be done even if they do not join the study. If the patient has had some of them recently, they may not need to be repeated. This will be up to the study doctor.

- Physical exam
- Blood tests
- Urine tests
- Kidney function tests
- Liver function tests
- Bone scan
- MRI of the head and neck (MRI is Magnetic Resonance Imaging, the use of magnetic waves to look at soft tissues of the body)
- CT scan of the chest (CT is Computed Tomography, a CT scan takes a picture of the inside of a patient's body)
- Pregnancy test (if patient is a female of childbearing potential)


During the study
If the exams, tests and procedures show that the patient can be in the study, and they choose to take part, then they will need the following tests and procedures. They are part of regular cancer care.

- Hearing tests
- Measurements of saliva production
- Dental x-rays
- Hormone and Growth/Development tests
- Imaging Studies (MRI and CT scans)
- Bone scans
- Kidney function tests

Patients will need these tests and procedures that are part of regular cancer care. They are being done more often because the patient is in this study.
- Hearing tests
- Measurements of saliva production
- Imaging Studies (MRI and CT scans)
- Bone scan
- Kidney function tests

Patients will need these tests and procedures to see how being on the study is affecting their body.
- Hearing tests
- Measurements of saliva production
- Dental x-rays
- Kidney function tests

Study Treatment
Patients will be treated in one of two ways depending on the stage of the disease:
- Treatment Group 1: Patients with early stages of disease will get radiation therapy only.
- Treatment Group 2: Patients with advanced disease, or disease that has spread, will first get chemotherapy alone and then get a combination of chemotherapy and radiation therapy.

Treatment Group 1
Patients will get radiation therapy to the head and neck five days a week for about seven or eight weeks. They will also get the drug amifostine every day before getting radiation therapy.
Amifostine will be given by an injection under the skin 15-30 minutes before radiation therapy starts. Some larger patients will get two doses a day.

Other drugs will be given to help prevent or manage any side effects that may be caused by the treatment. Also, because radiation causes thickened saliva and dry mouth, the patient will be given a drug (pilocarpine) that helps the production of saliva. Pilocarpine, along with mouth washes, will help to keep the patient's mouth moist and protect the patient from infections. Patients will also get fluoride to protect their teeth.

Treatment Group 2
Patients will first get Induction therapy, over a period of nine weeks, in order to shrink the tumor. Then they will get Consolidation therapy, also over a period of about nine weeks.

- Induction therapy is the use of chemotherapy to reduce/get rid of the cancer. If the cancer goes away then the disease will be in "remission".
- Consolidation therapy is treatment intended to make the cancer stay in remission.

In this study both chemotherapy and radiation therapy will be given.

The study doctor will evaluate the patient after Induction therapy and after Consolidation therapy. If he/she thinks that surgery could be used to remove the tumor then he/she will talk about it with the patient.

Induction therapy:
Induction therapy will be three cycles of chemotherapy. Each cycle will last 21 days. The patient will receive the drugs cisplatin (on Day 1 of each cycle) and 5-fluorouracil (on Days 1 to 4 of each cycle). These drugs have been used in the past for NPC and are likely to be the standard treatment, given even if the patient does not take part in this study. Other drugs will be given to help prevent or manage the side effects of the chemotherapy drugs, like nausea and vomiting.

Consolidation therapy
The chemotherapy part will be three cycles of cisplatin that last 21 days each. While the patient is getting chemotherapy they will also get radiation therapy to the head and neck area. This radiation therapy will be given five days a week for about seven to eight weeks.
The amount of radiation therapy the patient gets will depend upon how well the tumor responds to Induction therapy.

On the days the patient gets radiation therapy they will also get the drug amifostine. Amifostine will be given by an injection under the skin 15-30 minutes before radiation therapy starts. Some larger patients will get two doses a day.

Other drugs will be given to help prevent or manage any side effects that may be caused by the treatment. Drugs will be given to prevent nausea and vomiting that may occur after the patient gets cisplatin. Also, because radiation causes thickened saliva and dry mouth, the patient will be given a drug (pilocarpine) that helps the production of saliva. Pilocarpine, along with mouth washes, will help to keep the patient's mouth moist and protect the patient from infections. Patients will also get fluoride to protect their teeth.

When Finished With The Study Treatment
Patients will have a number of tests and procedures as part of their follow up to treatment. The research staff will use these tests to watch for improvements, monitor side effects and look for any signs that the cancer has come back.

Patients will have a physical exam and standard lab tests, including blood tests, plus scans (MRI and CT scans) of the affected area every three months during the first year after
treatment. These tests will only be done every six months for the second and third years after treatment. After three years the patient should have a physical exam and standard lab tests every year.

In addition to the tests to evaluate the cancer, patients will have other tests to monitor the effects of the treatment on their body. These tests will be done more often because the patient is taking part in this study:
- The research staff will measure the patient's saliva production at three, six and 12 months after treatment.
- Patients will have a hearing test at six and 12 months after treatment, and again after two and three years.
- The research staff will monitor the patient's growth and development by measuring certain hormone levels twice in the first year after treatment, and then once a year after that.
- A dental exam will be done every six months for the first year, and then once a year after that.
- Patients who are in Treatment Group 2 will also have a kidney function test at six and 12 months after therapy.

How long will the Study run?

Treatment Group 1: Patients will get radiation therapy for about seven to eight weeks. Then the study doctor will ask the patient to come back for follow-up exams for at least three years.

Treatment Group 2: Patients will get therapy for about 16 to 18 weeks. Then the study doctor will ask the patient to come back for follow-up exams for at least three years.

Both Treatment Groups: The research staff would like to continue to find out about the patient's health for about 10 years after the study closes to new patients. Researchers would like to do this by calling the patient on the telephone once a year to see how they are doing. Keeping in touch with the patient and checking on how their health is every year for a while after the study closes helps the research staff understand the long-term effects of the study.

Sponsor(s): Children's Oncology Group (COG)

Study Activation/Registration Date: 03/20/2008

IRB Review and Approval Date: 01/31/2008

Study Type: Treatment

Projected Accrual: The plan is to have up to 160 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Shakila P. Khan, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 05/13/2008