A Phase I Study of IMC-A12 (Anti-Insulin-Like Growth Factor-I Receptor Monoclonal Antibody) in Combination With CCI-779 (Temsirolimus) in Pediatric Patients With Recurrent or Refractory Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed solid tumor

- Recurrent or refractory disease

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

- Histologic confirmation not required for intrinsic brain stem tumors, optic
pathway gliomas, or pineal tumors with elevations of serum or CSF
alpha-fetoprotein or beta-HCG

- Slides or tissue blocks from either initial diagnosis or relapse must be
available

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

- Measurable or evaluable disease

- No known bone marrow involvement

- Patients with seizure disorder may be enrolled if on non-enzyme inducing
anticonvulsants and well controlled

- Neurologic deficits in patients with CNS tumors must have been clinically stable for
≥ the past week

PATIENT CHARACTERISTICS:

- Karnofsky performance status (PS) 50-100% (patients > 16 years of age) or Lansky PS
50-100% (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

- ANC ≥ 1,000/mm³*

- Platelet count ≥ 100,000/mm³* (transfusion independent)

- Hemoglobin ≥ 8.0 g/dL* (may receive RBC transfusions) NOTE: * Unless due to bone
marrow involvement by tumor.

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

- 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)

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

- ALT ≤ 110 U/L

- Serum albumin ≥ 2 g/dL

- Serum cholesterol and serum triglyceride levels < grade 2

- PT and INR < 1.2 times ULN

- Seizure disorder may be allowed provided well controlled on anticonvulsants

- Not pregnant or nursing

- Negative pregnancy test

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

- Random or fasting blood glucose normal for age

- No uncontrolled infection

- No known type I or II diabetes mellitus

- No patients who, in the opinion of the investigator, may not be able to comply with
the safety monitoring requirements of the study

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to cixutumumab or temsirolimus

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- See Patient Characteristics

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

- At least 2 months since prior stem cell transplant or rescue and no evidence of
active graft-versus-host-disease

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

- More than 6 weeks since prior major surgery

- Patients with history of recent minor surgical procedures (e.g., vascular
catheter placement, bone marrow evaluation, laparoscopic surgery) are eligible

- At least 7 days since prior hematopoietic growth factors that support platelet or
white cell number or function

- At least 7 days since prior therapy with a biologic (antineoplastic) agent

- At least 6 weeks since prior monoclonal antibodies

- Patients receiving corticosteroids must be on a stable or decreasing dose of
corticosteroid for the 7 days prior to enrollment

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

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

- At least 6 weeks since other prior substantial bone marrow radiation therapy

- No prior temsirolimus or monoclonal antibody therapy targeting IGF-1R

- No concurrent systemic warfarin for anticoagulation therapy

- Low-dose warfarin for maintaining patency of central venous catheter allowed

- No concurrent insulin or growth hormone therapy

- No concurrent enzyme-inducing anticonvulsants

- No concurrent potent CYP3A4 inducers or inhibitors (i.e., erythromycin,
clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice, or St.
John wort)

- No other concurrent investigational agents

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