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

Phase 2

Terminated

Conditions: Recurrent Uterine Sarcoma
Uterine Carcinosarcoma

Interventions: Drug: temsirolimus

Registration Number: NCT01061606

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 8

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (temsirolimus)	temsirolimus	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.

Primary Outcome Measures

Name	Time	Method
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	6 months from registration	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.

Secondary Outcome Measures

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

Trial Locations

Locations (20): Tower Cancer Research Foundation
🇺🇸
Beverly Hills, California, United States
City of Hope Medical Group Inc
🇺🇸
Pasadena, California, United States
Women's Cancer Care Associates LLC
🇺🇸
Albany, New York, United States
Los Angeles County-USC Medical Center
🇺🇸
Los Angeles, California, United States
City of Hope
🇺🇸
Duarte, California, United States
The Valley Hospital-Luckow Pavilion
🇺🇸
Paramus, New Jersey, United States
Morristown Memorial Hospital
🇺🇸
Morristown, New Jersey, United States
Penn State Hershey Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
Children's Hospital of New York Presbyterian
🇺🇸
New York, New York, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
New York University Langone Medical Center
🇺🇸
New York, New York, United States
Saint Luke's Roosevelt Hospital Center - Roosevelt Division
🇺🇸
New York, New York, United States
Columbia University College of Physicians and Surgeons
🇺🇸
New York, New York, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
University of California at Davis Cancer Center
🇺🇸
Sacramento, California, United States
Beth Israel Medical Center
🇺🇸
New York, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
Presbyterian-Weill Medical College
🇺🇸
New York, New York, United States
University of Connecticut
🇺🇸
Farmington, Connecticut, United States