Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This phase II trial is studying how well giving temsirolimus together with cixutumumab works in treating patients with locally advanced, metastatic, or recurrent soft tissue sarcoma or bone sarcoma. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving temsirolimus together with cixutumumab may kill more tumor cells

Further Study Information

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

Eligibility Criteria

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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Gary K. Schwartz

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01016015
Information obtained from ClinicalTrials.gov on February 18, 2013

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