IRB Number:

100-04

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

This study is being done to:
- Avoid chemotherapy in low risk testicular/ovarian germ cell tumors by using surgery and observation, and using chemotherapy only if the tumor comes back.
- Lower the total amount of chemotherapy cycles given (three times instead of four)
for those patients getting chemotherapy and find out the effects, good and/or bad.
- Lower the number of days over which the chemotherapy is given from five to three days.
A secondary goal of the study is to understand the biology of germ cell tumors better.
Researchers would like to know more about the genetic factors that affects the development of germ cell tumors.
Patients are being asked to take part in this study because they have been told that they have a germ cell tumor. A germ cell tumor is a type of cancer that happens in the ovaries (for females) or the testes (for males). This tumor may also be found in other areas of the
body such as the brain, chest or abdomen.
A germ cell tumor is considered low risk when it is present only in the testes or ovaries and is completely taken out by surgery.
A germ cell tumor is considered intermediate risk when:
- It is present only in the testes or ovary, but is not completely taken out by surgery.
- It is present in the testes or ovary and has spread to the lymph nodes or other organs.
- It is present only at one site outside the ovaries or testes, but may or may not be completely taken out by surgery.
The term, risk, refers to the chance of the cancer coming back after treatment.

The standard treatment for patients who have low risk testicular tumors is surgery to take out the tumor and observation; the standard treatment for patients with low risk ovarian tumors is surgery plus chemotherapy (cancer-fighting drugs) given for four cycles (with five days for each cycle of treatment).
The standard treatment for patients with intermediate risk germ cell tumors is surgery plus chemotherapy given for four cycles (with five days for each cycle of treatment).
Germ cell tumors are rare, and account for only 3 percent of all childhood cancers. However, the survival rate for patients with these types of tumors is very high at 95 percent for low risk tumors and 93 percent for intermediate risk tumors.
The standard treatment for germ cell tumors is very effective. Study doctors would like to know if it is possible to lower the side effects from chemotherapy treatment. Side effects are unintended or unwanted results. When chemotherapy is lowered, there have been fewer side effects from chemotherapy. This study will test if lowering the amount of chemotherapy given to intermediate risk tumor patients and not giving chemotherapy to low risk patients will result in the same high survival rate.

Who is Eligible to Participate in the Study?

-Age 21 years or less at diagnosis, except patients with testicular primary tumors, who must be less than 15 years of age.
-Diagnosed with germ cell tumor
-No previous chemotherapy or radiation therapy

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

What is Involved With this Study?

The initial treatment plan involves surgery to take out the germ cell tumor and then cancer fighting medicine called chemotherapy for intermediate risk patients. Chemotherapy treatment on this clinical trial takes either two and one half or four and one half months.

Before getting treatment
If patients take part in this study, they will have a number of standard medical tests and exams done before getting treatment so the doctor can tell if they have a low or intermediate risk germ cell tumor.

Surgery
After the initial medical tests, patients will have an operation to completely take out the tumor. If it is not possible to completely take out the tumor, a biopsy will be done. (A biopsy is taking out a small amount of tumor for examination under the microscope.) The results of the biopsy or surgery will be used to help tell if patients have a low or an intermediate risk germ cell tumor. This will determine the next part of their treatment.

Treatment for Low Risk Tumors
If patients have a low risk tumor, the only initial treatment will be surgery. After surgery, the research staff will watch the patient closely using X-rays and other scans and blood tests to measure the tumor markers.
If over time there is no evidence of disease (the tumor does not come back) and the tumor markers are normal, there will be no more treatment, but the research staff will keep on watching the patient.

If over time there is evidence of disease (a recurrence, which means the tumor has come back) or the tumor markers are not normal, patients will be treated with chemotherapy in the same manner that the intermediate risk patients are treated over a period of nine weeks.

Treatment for Intermediate Risk Tumors
If patients have an intermediate risk germ cell tumor (or a low risk tumor with evidence of disease after surgery or recurrence ) they will be treated with chemotherapy over a period of nine weeks.
Each treatment will have three anti-cancer drugs: cisplatin, etoposide, and bleomycin. Each chemotherapy treatment lasts three days. On the first day, the patient is given all three drugs directly into their vein (called "IV"). Bleomycin is given for ten minutes
and both cisplatin and etoposide are given for 90 minutes. On the second and third day of treatment, only the cisplatin and etoposide are given. As before, they are both
given directly into the vein for 90 minutes each day.

A schedule of the chemotherapy is outlined below:
Week 1 Day 1: Bleomycin, Cisplatin, Etoposide
Day 2: Cisplatin, Etoposide
Day 3: Cisplatin, Etoposide
Week 2 No drugs
Week 3 No drugs
Week 4 Day 1: Bleomycin, Cisplatin, Etoposide
Day 2: Cisplatin, Etoposide
Day 3: Cisplatin, Etoposide
Week 5 No drugs
Week 6 No drugs
Week 7 Day 1: Bleomycin, Cisplatin, Etoposide
Day 2: Cisplatin, Etoposide
Day 3: Cisplatin, Etoposide
Week 8 No drugs
Week 9 No drugs
Week 10 Evaluation

Following chemotherapy, the research staff will watch the patient closely. X-ray and other scans and blood tests to measure the tumor markers will be done often to see if the tumor has come back. The next part of the treatment will depend on how the patient responded to the chemotherapy.

No Change or tumor growth: If the tumor is the same or increased in size, or the tumor markers have increased, the patient will not stay on this treatment. Other
treatment options will be considered and these will be talked over with their physician.
No Evidence of Disease: If there is no sign of the tumor and the tumor markers are normal, patients will not get any more treatment. The research staff will keep on watching the patient closely.
Evidence of Disease: If the tumor is smaller in size but still there, the patient will be treated either with surgery alone, surgery plus chemotherapy, or chemotherapy
alone. If the tumor markers continue to not be normal, the patient will be treated with chemotherapy drugs. If chemotherapy is necessary a second time, the same drugs will be given on the same schedule as during the first phase of chemotherapy told about above.

Following surgery or chemotherapy, the research staff will keep on watching the patient closely. The medical tests described above will be done every now and then for two years following chemotherapy or surgery, and then will be done once a year.

How long will the Study run?

If patients have a low risk germ cell tumor, they will be on the study during surgery and follow-up observation. If a relapse happens, they will be treated with chemotherapy for
either two and one half or four and one half months.
If patients have an intermediate risk germ cell tumor they will have surgery and then will get chemotherapy for either two and one half or four and one half months.
The research staff would like to keep finding out about the patient's health for about 10 years after the study closes to new patients. Keeping in touch with the patient and checking on how their health is every year for a while after the study closes helps researchers understand the long-term effects of the study.

Sponsor(s): Children's Oncology Group

Study Activation/Registration Date: 02/25/2004

IRB Review and Approval Date: 02/05/2004

Study Type: Treatment

Projected Accrual: The plan is to have up to 306 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: Vilmarie Rodriguez, 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: 06/06/2008