Temsirolimus and Cixutumumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Soft Tissue Sarcoma or Bone Sarcoma

Inclusion Criteria:

• Histologically or cytologically confirmed sarcoma of soft tissue or bone

  • Metastatic and/or locally advanced or locally recurrent disease by physical exam or imaging

• Measurable disease by RECIST criteria

  • Measurable disease ('target' lesion) is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm by CT scan (CT scan slice thickness ≤ 5 mm) or calipers by clinical exam (lesions that cannot be accurately measured with calipers should be recorded as non-measurable) OR as ≥ 20 mm by chest x-ray
• Must have received and failed 1-3 prior chemotherapy regimens for recurrent/metastatic disease

• Patients at MSKCC must consent to tumor biopsies before treatment and after the second week of therapy

  • Patients who do not have accessible tumor for biopsy may be allowed at the discretion of the principal investigator
• Confirmation of IGF1R status in pre-existing tumor specimens by IHC
• Brain metastases allowed provided they were previously treated with definitive surgery or radiotherapy and have been clinically stable for 3 months following the procedure with no neurological signs or symptoms and no requirement for systemic glucocorticoids
• ECOG performance status 0 or 1
• ANC ≥ 1.5 times 10^9/L
• Platelet count ≥ 100 times 10^9/L
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (except for patients with known Gilbert syndrome)
• AST and ALT ≤ 2.5 times ULN
• Serum creatinine ≤ 1.5 times ULN

• Serum glucose ≤ 120 mg/dL (nonfasting or fasting)

  • No hyperglycemia, defined as fasting serum glucose > 120 mg/dL
• Fasting total cholesterol ≤ 300 mg/dL
• Fasting triglycerides ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No current evidence of another malignancy
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus, cixutumumab, or other agents used in the study

• No concurrent uncontrolled illness including, but not limited to, the following:

  • Known ongoing or active infection, including HIV or active hepatitis B or C infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia (e.g., atrial fibrillation or ventricular dysrhythmias [other than premature ventricular contractions])
  • Psychiatric illness/social situation that would limit compliance with study requirements
• No other concurrent anticancer agents or therapies
• Recovered from prior therapy
• At least 4 weeks since prior systemic therapy (including tyrosine kinase inhibitors) (6 weeks for carmustine or mitomycin C)

• More than 4 weeks since prior major surgery and recovered

  • Surgical changes that are not expected to improve (e.g., removal of muscle tissue) allowed

• More than 4 weeks since prior glucocorticoid therapy administered for > 5 days

  • Replacement glucocorticoids for pre-existing deficiency (e.g., Addison disease) allowed
• No prior IGFR1 inhibitors
• No prior mTOR inhibitors (e.g., sirolimus, everolimus, deforolimus, or temsirolimus)
• No concurrent oral anti-diabetic or insulin therapy
• No concurrent prophylactic hematopoietic colony-stimulating factors
• No other concurrent investigational agents