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

Study Overview
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Brief Summary
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This phase II trial is studying how well CCI-779 works in treating patients with soft tissue sarcoma or gastrointestinal stromal tumor. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description
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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.

Official Title
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A Trial of CCI-779 in Patients With Soft Tissue Sarcoma.

Conditions
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Gastrointestinal Stromal Tumor, Recurrent Adult Soft Tissue Sarcoma, Stage I Adult Soft Tissue Sarcoma, Stage II Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma

Intervention / Treatment
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* Drug: temsirolimus
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (temsirolimus)<br>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. | Drug: temsirolimus<br>* Given IV<br>* Other names: Torisel;Other: laboratory biomarker analysis<br>* Optional correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of confirmed tumor responses, defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart |  | Up to 6 months (6 courses) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time | The distribution of survival time will be estimated using the method of Kaplan-Meier. | Time from registration to death due to any cause, assessed up to 5 years | 
| Time to disease progression | The distribution of time to progression will be estimated using the method of Kaplan-Meier. | Time from registration to documentation of disease progression, assessed up to 5 years | 
| Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented |  | Up to 5 years | 
| Time to treatment failure |  | Time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 5 years |