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A Phase 2 Study of Temsirolimus (CCI-779, NSC 683864) and IGF-1 Receptor Antibody Cixutumumab (IMC-A12, NSC 742460) in Patients With Metastatic Sarcomas

Phase 2
18 Years
Open (Enrolling)
Metastatic Osteosarcoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Osteosarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma

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Trial Information

A Phase 2 Study of Temsirolimus (CCI-779, NSC 683864) and IGF-1 Receptor Antibody Cixutumumab (IMC-A12, NSC 742460) in Patients With Metastatic Sarcomas


I. To determine the proportion of patients progression-free at 12 weeks (PFS, defined as
RECIST 1.1 CR + PR + SD) with (A) IGF-1R+ soft tissue sarcomas; (B) IGF-1R+ bone tumors; or
(C) IGF-1R(-) sarcomas, who are treated weekly with intravenous A12 and temsirolimus.


I. To determine the overall response rate (defined as complete response [CR] + partial
response [PR]).

II. To determine the overall survival. III. To determine the correlation of clinical outcome
with pre- and post-treatment IGF-1R pathway related markers in plasma (pre and post
therapy), archived tissue, and pre- and post-treatment tumor biopsies.


Patients receive cixutumumab IV over 60 minutes and temsirolimus IV over 30 minutes on days
1, 8, 15, 22, 29, and 36. Courses repeat every 42 days in the absence of disease progression
or unacceptable toxicity.

After completion of study treatment, patients are followed up for ≥ 4 weeks.

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

- 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

- 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

- 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)

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival rate, defined as CR + PR + SD, as assessed by RECIST criteria

Outcome Description:

For each arm, the response rate will be estimated and a confidence interval will be constructed.

Outcome Time Frame:

12 weeks

Safety Issue:


Principal Investigator

Gary Schwartz

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2009

Completion Date:

Related Keywords:

  • Metastatic Osteosarcoma
  • Recurrent Adult Soft Tissue Sarcoma
  • Recurrent Osteosarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Osteosarcoma
  • Sarcoma



Memorial Sloan Kettering Cancer CenterNew York, New York  10021
M D Anderson Cancer CenterHouston, Texas  77030