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

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

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.

Study Overview

• Status: Terminated
• Conditions: Uterine Carcinosarcoma; Recurrent Uterine Sarcoma
• Intervention / Treatment: Drug: temsirolimus

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211-1850
      • Tower Cancer Research Foundation
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
    • Pasadena, California, United States, 91105
      • City of Hope Medical Group Inc
    • Sacramento, California, United States, 95817
      • University of California at Davis Cancer Center
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital-Luckow Pavilion
  • New York
    • Albany, New York, United States, 12208
      • Women's Cancer Care Associates LLC
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center - Moses Campus
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • New York, New York, United States, 10032
      • Columbia University College of Physicians and Surgeons
    • New York, New York, United States, 10019
      • Saint Luke's Roosevelt Hospital Center - Roosevelt Division
    • New York, New York, United States, 10021
      • Presbyterian-Weill Medical College
    • New York, New York, United States, 10032
      • Children's Hospital of New York Presbyterian
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Children's Hospital
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (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.	Drug: temsirolimus; Given IV; Other Names: Torisel; CCI-779; cell cycle inhibitor 779

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mark Einstein, Montefiore Medical Center - Moses Campus

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: February 2, 2010
• First Submitted That Met QC Criteria: February 2, 2010
• First Posted (Estimate): February 3, 2010

Study Record Updates

• Last Update Posted (Estimate): November 9, 2016
• Last Update Submitted That Met QC Criteria: September 21, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Neoplasms, Complex and Mixed; Sarcoma; Recurrence; Carcinosarcoma; Mixed Tumor, Mullerian; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: NCI-2012-02989 (Other Identifier: CTRP (Clinical Trial Reporting Program)); P30CA013330 (U.S. NIH Grant/Contract); N01CM00038 (U.S. NIH Grant/Contract); 8167 (Other Identifier: CTEP)