VEGF Receptor Tyrosine Kinase Inhibitor Axitinib in Children With Recurrent or Refractory Solid Tumors

Inclusion Criteria

- Age: Patients must be > than 12 months and < 18 years of age at the time of study
enrollment.

- Body Surface Area: Patients must have a BSA of ≥ 0.53 m2 at the time of study
enrollment.

- Diagnosis: Patients with refractory or recurrent solid tumors (excluding CNS tumors)
and patients with unresectable translocation positive renal cell carcinoma (tRCC) are
eligible. Patients must have had histologic verification of malignancy at original
diagnosis or relapse.

- The diagnosis of translocation morphology or TFE renal cell carcinoma is established
by having characteristic morphology AND either a) strong nuclear TFE3 or TFEb staining
on immunohistochemistry OR b) cytogenetic studies of the tumor demonstrating a TFE
translocation OR c) fluorescent in situ hybridization (FISH) demonstrating a TFE
translocation.

- Disease Status: Patients must have either measurable or evaluable disease

- Therapeutic Options: Patient's current disease state must be one for which there is no
known curative therapy or therapy proven to prolong survival with an acceptable
quality of life.

- Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for
patients ≤ 16 years of age . Patients who are unable to walk because of paralysis, but
who are up in a wheelchair, will be considered ambulatory for the purpose of assessing
the performance score.

- Prior Therapy

- Patients may have received bevacizumab, VEGF-Trap, or other VEGF blocking tyrosine
kinase inhibitors, but may not have received axitinib.

- Patients must have recovered from any VEGF blocking drug-related toxicity (e.g.,
proteinuria, hypertension).

- All patients must have fully recovered from the acute toxic effects of all prior
anti-cancer chemotherapy.

- Myelosuppressive chemotherapy: At least 21 days after the last dose of
myelosuppressive chemotherapy (42 days if prior nitrosourea).

- Hematopoietic growth factors: At least 14 days after the last dose of a long-acting
growth factor (e.g. Neulasta) or 7 days for short-acting growth factor. For agents
that have known adverse events occurring beyond 7 days after administration, this
period must be extended beyond the time during which adverse events are known to
occur. The duration of this interval must be discussed with the study chair.

- Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic
agent. For agents that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur. The duration of this interval must be discussed with the
study chair.

- Immunotherapy: At least 42 days after the completion of any type of immunotherapy,
e.g. tumor vaccines.

- Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a
monoclonal antibody.

- XRT: At least 14 days after local palliative XRT (small port); At least 150 days must
have elapsed if prior TBI, craniospinal XRT or if ≥ 50% radiation of pelvis; At least
42 days must have elapsed if other substantial BM radiation.

- Stem Cell Infusion without TBI: No evidence of active graft vs. host disease and at
least 84 days must have elapsed after transplant or stem cell infusion.

- Organ Function Requirements

- Adequate Bone Marrow Function Defined As:

- Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3

- Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)

Adequate Renal Function Defined As:

• Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or

Adequate Liver Function Defined as:

- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for
age

- SGPT (ALT) ≤ 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.

- SGOT (AST) ≤ 125 U/L. For the purpose of this study, the ULN for SGOT is 50 U/L.

- Serum albumin ≥ 2 g/dL.

Adequate Cardiac Function Defined As:

- Shortening fraction of ≥ 27% by echocardiogram, or Ejection fraction of ≥ 50% by gated
radionuclide study.

- Must not have a history of myocardial infarction, severe or unstable angina, or
peripheral vascular disease.

Adequate Blood Pressure Control Defined As:

A blood pressure (BP) ≤ the 95th percentile for age, height, and gender

Adequate Coagulation Defined As:

- No evidence of active bleeding

- PT and PTT ≤ 1.2 x upper limit of normal (ULN)

- INR ≤1.2

Adequate Pancreatic Function Defined as:

• Lipase ≤ 1.5 x upper limit of normal (ULN).

Exclusion Criteria

- Pregnancy or Breast-Feeding

- Corticosteroids: Patients receiving chronically dosed corticosteroids within 7 days
prior to enrollment are not eligible for this trial.

- Investigational Drugs: Patients who are currently receiving another investigational
drug are not eligible.

- Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are
not eligible.

- Anti-GVHD agents post-transplant:

Patients who are receiving cyclosporine, tacrolimus or other agents to prevent
graft-versus-host disease post bone marrow transplant are not eligible for this trial.

- CYP3A4/5 Inhibitors:

Patients chronically receiving drugs that are known potent CYP3A4/5 inhibitors within 7
days prior to study enrollment, including but not limited to ketoconazole, itraconazole,
clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir,
telithromycin, voriconazole, grapefruit, and grapefruit juice are not eligible

- CYP3A4/5 Inducers:

Patients chronically receiving drugs that are known potent CYP3A4/5 inducers within 7 days
prior to study enrollment, including but not limited to rifampin, dexamethasone, phenytoin,
carbamazepine, rifabutin, rifapentine, phenobarbital, and St John's wort are not eligible.

- Anti-hypertensives: Patients who are receiving anti-hypertensive medications for
control of blood pressure at the time of enrollment are not eligible for this trial.

- Anti-coagulation: Patients who are currently receiving therapeutic anti-coagulation
with heparin, low-molecular weight heparin or coumadin are not eligible for this
trial.

- Anti-inflammatory or anti-platelet agents: Patients who are currently receiving
aspirin, ibuprofen or other non-steroidal anti-inflammatory drugs or anti-platelet
agents are not eligible.

- Patients must be able to swallow tablets whole.

- Thyroid Replacement Therapy: Patients who require thyroid replacement therapy are not
eligible if they have not been receiving a stable replacement dose for at least 28
days prior to study enrollment. Patients who enter the study on thyroid replacement
should have their medication adjusted to maintain TSH in the normal range.

Bleeding and Thrombosis:

Patients with evidence of active bleeding, intratumoral hemorrhage, or bleeding diathesis
are not eligible:

- History (within 180 days prior to study enrollment) of arterial thromboembolic events,
including transient ischemic attack (TIA) or cerebrovascular accident (CVA).

- History (within 180 days prior to study enrollment) of pulmonary embolism, DVT, or
other venous thromboembolic event.

- History of hemoptysis within 42 days prior to study enrollment.

Surgery: Patients who have had or are planning to have the following invasive procedures
are not eligible:

- Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic
injury within 28 days prior to enrollment.

- Subcutaneous port placement or central line placement is not considered major surgery
but must be placed at least 3 days prior to enrollment for external lines and at least
7 days prior to enrollment for subcutaneous port.

- Core biopsy within 7 days prior to enrollment.

- Fine needle aspirate or central line placement within 7 days prior to enrollment.

CNS disease:

- Patients who have a known primary or metastatic CNS tumor at the time of study
enrollment are not eligible. A prior history of metastatic CNS tumor is allowed as
long as there is no evidence of CNS disease at study enrollment.

- Patients who have a serious or non-healing wound, ulcer, or bone fracture at the time
of study enrollment are not eligible.

- Patients who have a history of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess within 28 days of study enrollment are not eligible.

- Infection: Patients who have known HIV or an uncontrolled infection are not eligible.

- Patients who have received a prior solid organ transplantation are not eligible.