CCI-779 in Treating Patients With Soft Tissue Sarcoma or Gastrointestinal Stromal Tumor

PRIMARY OBJECTIVES:

I. To assess the antitumor activity of CCI-779 in this patient population.

SECONDARY OBJECTIVES:

I. To assess the following in patients with soft tissue sarcomas and following treatment with CCI-779: duration of response, time to progression, survival.

TERTIARY OBJECTIVES:

I. To describe and correlate the following with patient characteristics and outcome in this patient population and following treatment with CCI-779: relative levels of 4EBP1 to eIF4E, phospho 4EBP1, total and phospho ribosomal S6 on pretreatment tumor tissue, expression levels of EGFR, activated EGFR, Her2, c-Myc, phospho Akt, total Akt, phospho-mTOR and total mTOR on pretreatment tumor tissue, drug induced inhibition of p70S6 kinase activity, and phosphorylation of S6 in PBMC, relative levels of serum sirolimus in post-treatment samples.

OUTLINE:

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses beyond CR.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years.

Inclusion criteria

• Histologically or cytologic confirmed soft tissue sarcoma
• Measurable disease; for patients having only lesions measuring at least 1 cm to less than 2 cm, must use spiral CT imaging for both pre- and post-treatment tumor assessments
• Absolute neutrophil count (ANC) >= 1,500/μL
• Platelets (PLTS) >= 100,000/μL
• Hgb >= 10.0 g/dL
• Direct bilirubin =< 1.5 x ULN (upper limit normal)
• AST(SGOT) =< 2.5 x ULN or =< 5 x ULN* if liver metastases are present
• ALT(SGPT) =< 2.5 x ULN or =< 5 x ULN* if liver metastases are present
• Creatinine =< 1.5 x ULN, or if greater, creatinine clearance >= 50 mL/min/1.73 m^2
• Baseline glucose levels
• Fasting serum cholesterol =< 350 mg/dL (9.0 mmol/L)
• Fasting triglycerides =< 400 mg/dL (4.56 mmol/L)
• ECOG Performance Status (PS) 0, 1 or 2
• Life expectancy >= 12 weeks
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent

Exclusion criteria

• Any of the following as this regimen may be harmful to a developing fetus or nursing child:

• Pregnant women
• Breast-feeding women
• Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception ( diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
• Any of the following:

• Nitrosoureas or mitomycin =< 6 weeks prior to study entry
• Other chemotherapy =< 4 weeks prior to study entry
• Radiotherapy =< 4 weeks prior to study entry
• Concurrent use of any other investigation agent
• Adverse events due to agents administered =< 4 weeks prior to study entry
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CCI-779
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, diabetes, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known HIV-positive patients receiving combination anti-retroviral therapy
• Prior chemotherapy for metastatic disease

• Exceptions:

• Patients with GIST who fail Gleevec are eligible
• Patients who have had adjuvant/neoadjuvant chemotherapy are also eligible
• Known brain metastases

• Exception: Patients with treated brain metastatic disease with stable symptoms after treatment for >= 1 month