Temsirolimus in Treating Patients With Recurrent or Persistent Cancer of the Uterus

Study Overview
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Brief Summary
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This phase II trial is studying how well temsirolimus works in treating patients with recurrent or persistent cancer of the uterus. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the efficacy of Temsirolimus in women with recurrent or persistent (after primary therapy) Carcinosarcoma (MMMT) of the uterus. II. Assess the safety and tolerability of Temsirolimus in this patient population. III. Evaluate secondary efficacy endpoints of time to tumor progression, progression-free survival (PFS), 6 month PFS rate, and duration of response. SECONDARY OBJECTIVES: I. Overall survival II.Duration of Response III. Time to progression IV. Time to treatment failure OUTLINE: This is a multicenter study. Patients receive temsirolimus 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. After completion of study therapy, patients are followed up periodically for up to 3 years.

Official Title
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Pilot Phase II Study of Temsirolimus in Patients With Recurrent Mixed Mesodermal and Mullerian Tumors (Carcinosarcoma) of the Uterus

Conditions
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Uterine Carcinosarcoma, Recurrent Uterine Sarcoma

Intervention / Treatment
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* Drug: temsirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed Carcinosarcoma (MMMT) Measurable disease; Only one prior systemic treatments after primary adjuvant treatment for persistent or metastatic disease are permitted, Radiation therapy (adjuvant or palliative) must be completed ≥ 4 weeks prior to registration Required laboratory values obtained =< 7 days prior to registration: Absolute Neutrophil Count (ANC) >= 1500/mm^3 Platelets >= 75,000/mm^3 Hemoglobin >= 9.0 g/dL Direct bilirubin =< 1.5 x upper limit of normal (ULN) Alkaline phosphatase =< 2.5 x ULN (≤ 5 x ULN if liver metastasis is present) SGOT(AST) =< 2.5 x ULN (≤ 5 x ULN if liver metastasis is present) Creatinine =< 1.5 x ULN Fasting serum cholesterol ≤ 350mg/dL (9.0 mmol/L) Triglycerides ≤ 1.5 x ULN Patients with Triglyceride levels > 1.5 x ULN can be started on lipid lowering agents and reevaluated within 1 week; if levels go to ≤ 1.5 x ULN, they can be considered for the trial and continue the lipid lowering agents International Normalized Ratio (INR) ≤ 1.5 (unless the patient is on full dose warfarin) ECOG Performance Status (PS) 0-1 Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent Full-dose anticoagulants, if a patient is receiving full-dose anticoagulants, the following criteria should be met for enrollment: The subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin Patients who have had prior anthracycline must have a normal ejection fraction on LVEF assessment by MUGA or Echo ≤ 4 weeks prior to registration Availability of tissue samples or blocks (from the primary tumor or metastases) for tumor studies Willingness to donate blood for correlative marker studies Exclusion Criteria: Prior therapy with Temsirolimus or another mTOR inhibitors Patients cannot be receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) nor any other CYP3A4 inducer such as rifampin or St. John's wort Untreated central nervous system (CNS) metastases; exceptions: patients with known CNS metastases can be enrolled if the brain metastases have been adequately treated and there is no evidence of progression or hemorrhage after treatment as ascertained by clinical examination and brain imaging (MRI or CT) ≤ 12 weeks prior to registration and no ongoing requirement for steroids Anticonvulsants (stable dose) are allowed Patients who had surgical resection of CNS metastases or brain biopsy ≤ 3 months prior to registration will be excluded Pregnant or lactating wome Currently active, second malignancy other than non-melanoma skin cancers; - Other uncontrolled serious medical or psychiatric condition (e.g. cardiac arrhythmias, diabetes, etc.) Active infection requiring antibiotics Received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer Radiation therapy to > 50% of marrow bearing areas

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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 temsirolimus 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. | Drug: temsirolimus<br>* Given IV<br>* Other names: Torisel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Rate, in Terms of the Proportion of Confirmed Tumor Responses (CR or PR) Assessed Using RECIST |  | Up to 3 years | 
| Progression Free Survival | The 6-month progression-free rate is defined as the total number of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration divided by the total number of efficacy-evaluable patients enrolled on study. | 6 months from registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time to event distributions will be estimated using the Kaplan-Meier method. | From registration to death, assessed up to 3 years | 
| Duration of Response, 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 | Median duration of response and the confidence interval for the median duration will be computed. | Up to 3 years | 
| Time to Treatment Failure | Time to treatment failure will be evaluated using the method of Kaplan-Meier. | From study registration to the date patients end treatment, assessed up to 3 years | 
| Time to Progression |  | Time to progression is defined as the time from registration to disease progression. |