Study of Kidney Tumors in Younger Patients

PRIMARY OBJECTIVES:

I. Classify patients with renal tumors by histological categorization, surgico-pathological
stage, presence of metastases, age at diagnosis, tumor weight, and loss of heterozygosity for
chromosomes 1p and 16q, to define eligibility for a series of therapeutic studies. (Loss of
heterozygosity [LOH] testing discontinued as of April 2014) II. Maintain a biological samples
bank to make specimens available to scientists to evaluate additional potential biological
prognostic variables and for the conduct of other research by scientists.

SECONDARY OBJECTIVES:

I. Monitor outcome for those patients who are not eligible for a subsequent therapeutic
study.

II. Describe whether the pulmonary tumor burden correlates with outcome in stage IV patients.

III. Describe the sensitivity and specificity of abdominal computed tomography (CT) by
comparison with surgical and pathologic findings for identification of local tumor spread
beyond the renal capsule to adjacent muscle and organs, lymph node involvement at the renal
hilum and in the retroperitoneum, preoperative tumor rupture, and metastases to the liver.

IV. Compare the sensitivity and specificity of pre-operative abdominal CT scan and magnetic
resonance imaging (MRI) for the identification and differentiation of nephrogenic rests and
Wilms' tumor in children with multiple renal lesions.

V. Correlate the method of conception (natural vs assisted reproductive technology) with the
development of Wilms' tumor.

VI. To evaluate the frequency of integrase interactor 1 (INI1) mutations in renal and
extrarenal malignant rhabdoid tumor of the kidney and to determine the incidence of germline
and inherited versus somatic mutations to facilitate clinical correlations on the companion
study AREN0321. (INI1 testing discontinued as of April 2014)

OUTLINE:

Tumor tissue, blood, and urine samples are collected for research studies, including
immunohistochemistry. CT scans and MRIs are also performed. Loss of heterozygosity analyses
(chromosome 1p and 16q) are performed by extraction of DNA. DNA polymorphisms are assayed by
polymerase chain reaction using standard methodology. Leftover specimens are archived for
future studies. (LOH and INI1 testing discontinued as of April 2014)

Patients are followed up periodically for 5 years.

Inclusion Criteria:

- Patients with the first occurrence of any tumor of the kidney identified on CT scan or
MRI are eligible for this study; histologic diagnosis is not required prior to
enrollment but is required for all patients once on study

- Eligible tumors include (but are not limited to):

- Nephroblastic tumors

- Nephroblastoma (Wilms' tumor) (favorable histology, anaplasia [diffuse,
focal])

- Nephrogenic rests and nephroblastomatosis

- Cystic nephroma and cystic partially differentiated nephroblastoma

- Metanephric tumors (metanephric adenoma, metanephric adenofibroma,
metanephric stromal tumor)

- Mesoblastic nephroma (cellular, classic, mixed)

- Clear cell sarcoma

- Rhabdoid tumor (any malignant rhabdoid tumor occurring outside the central
nervous system [CNS])

- Renal epithelioid tumors of childhood (papillary renal cell carcinoma, medullary
renal cell carcinoma, renal tumors associated with Xp11.2 translocations,
oncocytic renal neoplasms after neuroblastoma)

- Angiolipoma

- Ossifying renal tumor of infancy

- Patients with the first occurrence of the following tumors are also eligible:

- Extrarenal nephroblastoma or extrarenal neprogenic rests

- Malignant rhabdoid tumor occurring anywhere outside the Central Nervous System

- Required specimens, reports, and copies of imaging studies must be available for
submission or must become available during the required timeframe

- For ALL patients (with exception of bilateral, bilaterally predisposed or unilateral
tumor in solitary kidney planning to enroll without biopsy), the following submissions
are required:

- A complete set of recut hematoxylin and eosin (H & E) slides**

- Representative formalin-fixed paraffin-embedded tissue block or if a block is
unavailable, 10 unstained slides from a representative block of tumor**

- Institutional pathology report, transmittal form and pathology checklist

- Copies of images and institutional reports of CT and/or MRI abdomen and pelvis

- Copies of images and institutional report of CT chest for all malignant tumors

- Institutional surgical report(s)

- Tissue must be from diagnosis, prior to any chemotherapy or radiation

- For patients with clinical features and required imaging findings consistent with the
eligibility for the bilateral study, AREN0534 (or successor study), confirmed by
central review, biopsy is not required; however, if biopsy is done, tissue must be
submitted as for other renal tumors, and initial risk assignment will require
pathology and surgical rapid central reviews; transmittal form and pathology checklist
are also needed

- Patients with extrarenal Wilms tumor must have tumor tissue available for central
review

- Patients with extra-CNS malignant rhabdoid tumor must have tumor tissue available for
central review

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met