A Phase II 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 malignant solid tumor, including the following:

- Osteosarcoma

- Ewing sarcoma/peripheral primitive neuroectodermal tumor

- Rhabdomyosarcoma

- Neuroblastoma

- Wilms tumor

- Synovial sarcoma

- Hepatoblastoma

- Adrenocortical carcinoma

- Retinoblastoma

- No known curative therapy or therapy proven to prolong survival with an acceptable
quality of life exists

- Radiographically measurable disease*, defined as ≥ 1 unidimensionally measurable
lesion ≥ 20 mm by MRI or CT scan or ≥ 10 mm by spiral CT scan

- The following are not considered measurable disease:

- Ascites, pleural effusions, or other malignant fluid collections

- Bone marrow infiltration by tumor

- Lesions detected only by non-MIBG nuclear medicine studies (e.g., bone
scan)

- Previously irradiated lesions that have not demonstrated clear progression
post-radiotherapy

- No known CNS metastases unless they were treated by surgery or radiotherapy AND are
stable with no recurrent lesions for ≥ 3 months

- Lansky or Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2

- ANC ≥ 1,000/mm³ (> 250/mm³ for patients with neuroblastoma)

- Platelet count ≥ 75,000/mm³ (> 25,000/mm³ for patients with neuroblastoma)
(transfusion independent)

- Hemoglobin ≥ 8.0 g/dL (≥ 7.5 g/dL for patients with neuroblastoma) (RBC transfusion
allowed)

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

- ≤ 0.4 mg/dL (for patients 1 to 5 months of age)

- ≤ 0.5 mg/dL (for patients 6 to 11 months of age)

- ≤ 0.6 mg/dL (for patients 1 year of age)

- ≤ 0.8 mg/dL (for patients 2 to 5 years of age)

- ≤ 1 mg/dL (for patients 6 to 9 years of age)

- ≤ 1.2 mg/dL (for patients 10 to 12 years of age)

- ≤ 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

- ≤ 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)

- Total bilirubin ≤ 1.5 times upper limit of normal for age

- ALT ≤ 110 U/L

- Serum albumin ≥ 2 g/dL

- Blood glucose normal

- Not pregnant or nursing

- Negative pregnancy test

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

- Able to comply with safety monitoring requirements of study

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to study drug

- No uncontrolled infection

- No known type I or II diabetes mellitus

- Recovered from prior chemotherapy, immunotherapy, or radiotherapy

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

- At least 7 days since prior hematopoietic growth factors (14 days for pegfilgrastim)

- At least 6 weeks since prior monoclonal antibody therapy

- At least 7 days since other prior antineoplastic biologic agents

- No prior monoclonal antibody targeting the IGF-IR

- No prior small molecule kinase inhibitors of IGF-IR

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

- At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or
radiotherapy to ≥ 50% of the pelvis

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

- At least 2 months since prior stem cell transplantation

- No evidence of graft-versus-host disease

- Concurrent corticosteroids allowed provided dose is stable or decreasing over the
past 7 days

- Intermittent use of corticosteroids to manage infusional reactions allowed

- No other concurrent anticancer therapy, including chemotherapy, radiotherapy,
immunotherapy, or biologic therapy

- No other concurrent investigational agents

- No concurrent insulin or growth hormone therapy