Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors

OBJECTIVES:

Primary

- To determine the response rate in patients with relapsed or refractory malignant solid
tumors treated with cixutumumab.

- To further define and describe the toxicities of this drug in these patients.

Secondary

- To examine the relationship between tumor expression of IGF-I, IGF-II, and IGF-IR and
response in patients treated with this drug.

- To determine the human anti-human antibody response in these patients after treatment
with this drug.

- To further evaluate the effect of this drug on circulating levels of proteins involved
in linear growth and glucose homeostasis, including IGF-I, IGF-II, IGF-BP3, growth
hormone, insulin, and C-peptide.

OUTLINE: This is a multicenter study. Patients are stratified according to disease type.

Patients receive cixutumumab IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats
every 28 days for up to 24 courses in the absence of disease progression or unacceptable
toxicity.

Patients undergo blood sample collection periodically for correlative laboratory studies.
Samples are analyzed for IGF-I, IGF-II, IGF-BP3, growth hormone, insulin, and C-peptide
levels and for immunogenicity.

DISEASE CHARACTERISTICS:

- 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 NOTE: *Measurable disease is not required for patients
with neuroblastoma; patients with MIBG+ evaluable neuroblastoma are
eligible

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

PATIENT CHARACTERISTICS:

- 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

PRIOR CONCURRENT THERAPY:

- 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