CCI-779 in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

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

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the overall survival at 6 months in patients with locally advanced or metastatic pancreatic cancer treated with CCI-779. SECONDARY OBJECTIVES: I. Determine time to progression, progression-free survival, overall survival, and tumor response rate in patients with measurable disease treated with this drug. II. Correlate biomarkers of response with clinical response in patients treated with this drug. III. Determine the safety and toxicity of this drug in these patients. OUTLINE: This is an open-label study. Patients receive CCI-779 IV over 30 minutes once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 13 months.

Official Title
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Phase II Trial of CCI-779 in Locally Advanced or Metastatic Pancreatic Cancer

Conditions
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Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer

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 cytologically confirmed adenocarcinoma of the pancreas Locally advanced or metastatic disease Radiographic evidence of disease No known brain metastases Performance status - ECOG 0-2 More than 3 months WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present) Creatinine ≤ 1.5 mg/dL Creatinine clearance ≥ 50 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Fasting serum cholesterol ≤ 350 mg/dL Fasting triglycerides ≤ 400 mg/dL No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other concurrent uncontrolled illness No concurrent prophylactic hematopoietic colony-stimulating factors No prior chemotherapy for metastatic pancreatic cancer More than 2 months since prior adjuvant or neoadjuvant chemoradiotherapy for resected pancreatic cancer Must have radiographic evidence of recurrent disease More than 2 months since prior chemoradiotherapy for locally advanced pancreatic cancer Must have radiographic evidence of disease progression See Chemotherapy See Chemotherapy No other concurrent investigational or commercial agents or therapies for the malignancy No other concurrent anticancer therapy No concurrent combination antiretroviral therapy for HIV-positive patients

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 once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | Drug: temsirolimus<br>* Given IV<br>* Other names: Torisel;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The method of Thall and Simon will be employed. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate defined as the number of patients who achieved CR or PR divided by the number of patients treated | 95% confidence interval will be presented | Up to 2 years | 
| Duration of response |  | From the time of objective response to the time of progressive disease, assessed up to 2 years | 
| Time to progression (TTP) |  | From the time of the study entry to the time of relapse or progression, assessed up to 2 years | 
| Systemic and local adverse events assessed using the established National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) | Descriptive statistics (mean, standard deviation, median, and range) will be displayed for relevant laboratory parameters. | Up to 2 years | 
| Levels of PTEN, AKT, and PI3K | Expression levels will be correlated with patient survival duration using Cox proportional hazard regression analysis | Up to 2 years | 
| Expression and phosphorylation status of p70s6k | Descriptive statistics will be applied to report the mean, duration of the effects on p70s6k phosphorylation. | Up to 7 days |