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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01061606
First received: February 2, 2010
Last updated: September 5, 2014
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Recurrent Uterine Sarcoma
Uterine Carcinosarcoma
Drug: temsirolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Phase II Study of Temsirolimus in Patients With Recurrent Mixed Mesodermal and Mullerian Tumors (Carcinosarcoma) of the Uterus

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tumor response rate, in terms of the proportion of confirmed tumor responses (CR or PR) assessed using RECIST [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Progression free survival rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Time to event distributions will be estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: From registration to death, assessed up to 3 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Median duration of response and the confidence interval for the median duration will be computed.

  • Time to progression [ Time Frame: From registration to disease progression, assessed up to 3 years ] [ Designated as safety issue: No ]
    Time to event distributions will be estimated using the Kaplan-Meier method.

  • Time to treatment failure [ Time Frame: From study entry to the date patients end treatment, assessed up to 3 years ] [ Designated as safety issue: No ]
    Time to treatment failure will be evaluated using the method of Kaplan-Meier.


Enrollment: 28
Study Start Date: January 2010
Study Completion Date: October 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel

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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed Carcinosarcoma (MMMT)
  • Patients must have measurable disease; Patients having only lesions measuring ≥ 1 cm to < 2 cm must use spiral CT imaging for both pre- and post-treatment tumor assessments; patients who have had prior palliative radiotherapy to metastatic lesion(s) must have at least one measurable lesion(s) that have not been previously irradiated
  • Only one prior systemic treatments after primary adjuvant treatment for persistent or metastatic disease are permitted, including targeted therapies, biologic response modifiers, chemotherapy, hormonal therapy or investigational therapy; for example, if a patient recurred after receiving radiation therapy and adjuvant ifosfamide or platinum based regimen, then was treated with Doxil and progressed, she is eligible; or, if a patient had stage 4 MMT cytoreduced followed by ifosfamide or platinum based regimen, then was treated with Doxil and progressed, she is eligible; NOTE: Hormonal therapy must be discontinued one week prior to registration; all other therapies must be discontinued at least 3 weeks prior to registration
  • 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
  • Negative serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only; NOTE: Patients and their partners should be practicing an effective form of contraception during the study and for at least 3 months following the last dose of this combined therapy
  • 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
  • Currently active, second malignancy other than non-melanoma skin cancers; NOTE: Patients are not considered to have a 'currently active' malignancy if they have completed anti-cancer therapy and are considered by their physician to be at less than 30% risk of relapse
  • Any of the following, as this regimen may be harmful to a developing fetus or nursing child:

    • Pregnant women
    • Breastfeeding 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.)
  • NOTE: The effects of the agent(s) on the developing human fetus at the recommended therapeutic dose are unknown
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01061606

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

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01061606     History of Changes
Other Study ID Numbers: NCI-2012-02989, NCI-2012-02989, AECM-8167, 8167, 8167, N01CM00038, P30CA013330
Study First Received: February 2, 2010
Last Updated: September 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinosarcoma
Mixed Tumor, Mullerian
Uterine Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Connective and Soft Tissue
Sarcoma
Urogenital Neoplasms
Uterine Diseases
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014