The iCat2, GAIN (Genomic Assessment Informs Novel Therapy) Consortium Study

Patients with extra-cranial (not in the brain) solid tumors that are either difficult to
diagnose or more difficult to treat are eligible to participate in this study. All enrolled
patients will have targeted sequencing of tumor performed. Sequencing results will be
reviewed for clinically significant findings including determination of whether any mutations
exist that suggest potential for activity of a targeted therapy (iCat recommendation).
Results will be returned to the patient's oncologist and follow-up data will be collected.

In this prospective multi-center cohort study, the primary objective is to describe the
outcomes of pediatric patients with advanced solid tumors according to whether or not they
received of targeted therapy matched to an iCat recommendation. The primary clinical outcome
of interest is the endpoint of overall survival (OS), with progression-free survival and
response rate (RR) as key secondary clinical outcome measures. To address this hypothesis,
825 patients will enroll from an anticipated 11 participating institutions over 3 years.

Inclusion Criteria:

- Age -- Age ≤ 30 years at time of initial qualifying solid tumor diagnosis

- Diagnosis -- Histologic diagnosis of solid malignancy (excluding brain tumors and
lymphoma) that meets at least one of the following criteria:

- Refractory, defined as tumor progression after initiation of standard first line
therapy without having achieved a prior partial or complete remission OR Biopsy
proven residual disease at the completion of planned standard initial front-line
therapy.

- Recurrent, defined as tumor progression after achieving a prior partial or
complete remission

- Newly diagnosed high risk disease, defined as having an expected event free
survival of < 50% at 2 years.

- Lacks definitive diagnosis or classical genomic findings after histologic review
and standard molecular testing (rare tumor group).

- Examples include (eligibility not limited to these examples):

- Histology typically associated with a fusion in which fusion is not detected.

- Ewing-like sarcoma

- Undifferentiated sarcoma

- Inflammatory myofibroblastic tumor without ALK fusion

- Infantile fibrosarcoma without NTRK fusion

- Specimen Samples

- Sufficient tumor specimen available to meet the minimum requirements for
profiling from diagnosis or progression / recurrence

--- OR

- Surgery / biopsy planned as part of clinical care that is anticipated to yield
sufficient material to meet the minimum requirements for profiling; OR

- Patient has already had molecular profiling and patient has not yet started
matched targeted therapy based on the report .

Exclusion Criteria:

- No Therapy Planned

-- Patients who have declined further anticancer therapy will be excluded.

- Performance Status

-- Patients with Lansky (age < 16 years) or Karnofsky (age ≥16 years) score < 50 will
be excluded.

- Life Expectancy -- Patients with anticipated life expectancy < 3 months will be
excluded.