AREN0532, Treatment for Very Low, Low and Standard Risk Favorable Histology Wilms Tumor

Summary

The following screening tests will be done prior to starting this study.

* A medical history

* Physical examination, including vital signs (blood pressure, pulse, temperature) height and weight

* Urine test to measure how the kidneys are functioning

* Blood tests to evaluate liver, kidney, metabolic function (the chemical and physical changes occurring in the body)

* Test to measure heart function (for patients assigned to stratum DD4A)

* Blood count (numbers of red and white cells and platelets)

* Radiological or imaging tests (such as CT scan, MRI, ultrasound and/or X-rays)

* Pregnancy test, if applicable

Subjects with very low risk Stage I Wilms tumor will have surgery alone. They will not receive chemotherapy and will be closely observed. The research part of the study is to see if the subjects will remain in remission.

Subjects with Stage I or II Wilms tumor who have the LOH change will get therapy over a period of about 25 weeks with the two standard drugs vincristine and dactinomycin plus the drug doxorubicin. This is called Regimen DD-4A. Radiation therapy will not be given. The research part of the study is to see if adding doxorubicin will make the cancer go away for as long as possible.

Subjects with Stage III Wilms tumor who do not have the LOH change will get standard therapy with Regimen DD-4A as above for a period of about 25 weeks, plus radiation therapy. This standard treatment and its risks are described in Attachments 1 and 2. The research part of the study is to see if there are things about the tumor cells that might tell us which subjects might have their disease return, or relapse, after the standard therapy.

Subjects with Stage III Wilms tumor who are found to have the LOH change will not stay on this study. They can enroll on another COG study, AREN0533, or they can discuss other treatment options with their doctor.

Subjects with local or distant relapse not involving the opposite kidney will get therapy that contains the three standard drugs (vincristine, dactinomycin and doxorubicin). This is called Regimen DD-4A. Therapy will be given over a period of about 25 weeks. Radiation therapy will be given to sites of metastatic tumor at the start of chemotherapy. Regimen DD-4A is used for other higher risk Wilms tumors.

Subjects with relapse in the remaining kidney will get standard therapy with Regimen DD-4A but no radiation therapy unless we are unable to fully remove the relapsed tumor.

Participant Eligibility

Patients must have previously enrolled on AREN0B32 (IRB File# 032006 048) and be found to have newly diagnosed Stage I-III favorable histology Wilms tumor, confirmed by central pathology and radiology review.
a) Patients will be eligible for the very low risk arm (surgery and observation only) if they have Stage I, Favorable Histology Wilms tumor, are < 2 yrs of age, and have a tumor weight < 550 g. They also must have had adequate submission of regional lymph nodes demonstrating histologically nodes negative for tumor and confirmation of absence of pulmonary metastases on CT scan of chest by central radiology review.
b) Patients will be eligible for the standard risk arm (DD4A) with no radiotherapy, if they have Loss of Heterozygosity for 1p and 16q, AND are either Stage I, Favorable Histology, Wilms tumor (age ≥ 2 years or tumor weight of ≥ 550 g), or Stage II, Favorable Histology, Wilms tumor with of any weight of tumor or patient age.
c) Patients will be eligible for the standard risk arm (DD4A) with radiotherapy, if they have no Loss of Heterozygosity for 1p and 16q and have Stage III, Favorable Histology Wilms tumor.
Specimens/materials must be submitted for central review by Day 7 at the latest. The Karnofsky performance status must be ≥ 50 for patients >16 years of age and the Lansky performance status must be ≥ 50 for patients ≤ 16 years of age. No prior tumor -directed chemotherapy or radiotherapy is acceptable. Adequate liver function. For patients assigned to Standard risk stratum (DD-4a): Adequate cardiac function. Female patients of childbearing potential must have a negative pregnancy test. Female patients who are lactating must agree to stop breast-feeding. Sexually active patients of childbearing potential must agree to use effective contraception. All patients and/or their parents or legal guardians must sign a written informed consent. All institutional, FDA, and NCI requirements for human studies must be met.