A Phase I Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, IND #100947, NSC #742460) in Children With Relapsed/Refractory Solid Tumors

Inclusion Criteria:

- Histologically confirmed solid tumor

- Relapsed or refractory disease

- No central nervous system (CNS) tumor or lymphoma

- Histological confirmation may have been made at original diagnosis or at relapse

- 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

- Measurable or evaluable disease

- Patients with Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET) must
have tissue blocks or slides available

- Study chair must be notified if tissue blocks or slides are not available

- Karnofsky performance status (PS) ≥ 50% (patients > 10 years of age) and Lansky (PS)
≥ 50% (patients ≤ 10 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

- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on
age/gender as follows:

- 1 to < 2 years (males and females 0.6 mg/dL)

- 2 to < 6 years (males and females 0.8 mg/dL)

- 6 to < 10 years (males and females 1.0 mg/dL)

- 10 to < 13 years (males and females 1.2 mg/dL)

- 13 to < 16 years (males 1.5 mg/dL and females 1.4 mg/dL)

- ≥ 16 years (males 1.7 mg/dL and females 1.4 mg/dL)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

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

- Serum albumin ≥ 2 g/dL

- Patients with known bone marrow metastatic disease will be eligible for study but not
evaluable for hematologic toxicity

- Patients must not be known to be refractory to red cell or platelet transfusion

- Patients with solid tumors without bone marrow involvement must meet the following
criteria:

- Peripheral absolute neutrophil count ≥ 1,000/μL

- Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving
platelet transfusions within a 7 day period prior to enrollment)

- Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study therapy

- No uncontrolled infection

- No known type I or type II diabetes mellitus

- Able to comply with the safety monitoring requirements of the study, in the opinion
of the investigator

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to IMC-A12

- Fully recovered from the acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study

- At least 7 days since prior and no concurrent hematopoietic growth factors

- Growth factors that support platelet or white cell number or function can only
be administered for culture-proven bacteremia or invasive fungal infection

- At least 7 days since prior and no concurrent biologic antineoplastic agents

- At least 6 weeks since prior monoclonal antibodies

- At least 3 months since prior total body irradiation (TBI), craniospinal external
radiotherapy (XRT), or ≥ 50% radiotherapy to the pelvis

- At least 2 weeks since prior local XRT (small port)

- At least 6 weeks since other prior substantial bone marrow radiotherapy

- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)

- More than 7 days since prior and no concurrent systemic corticosteroids

- Prior stem cell transplant or rescue allowed provided there has been no evidence of
active graft-versus-host-disease within the past 2 months

- No prior monoclonal antibody therapy targeting the IGF-IR

- No concurrent chemotherapy, radiotherapy, or immunotherapy

- No concurrent anticancer agents

- No concurrent insulin or growth hormone therapy

- No other concurrent investigational drugs