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

Uterine Carcinosarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01061606
• Other study ID #: NCI-2012-02989
• Secondary ID: NCI-2012-02989AE
• Status: Terminated
• Phase: Phase 2
• First received: February 2, 2010
• Last updated: September 5, 2014
• Start date: January 2010
• Est. completion date: October 2012

Study information

• Verified date: December 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: October 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinosarcoma
• Mixed Tumor, Mullerian
• Recurrent Uterine Sarcoma
• Uterine Carcinosarcoma
• Uterine Neoplasms

Intervention

Drug:
• temsirolimus
Given IV

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor response rate, in terms of the proportion of confirmed tumor responses (CR or PR) assessed using RECIST		Up to 3 years	No
Primary	Progression free survival rate	Time to event distributions will be estimated using the Kaplan-Meier method.	6 months	No
Secondary	Overall survival	Time to event distributions will be estimated using the Kaplan-Meier method.	From registration to death, assessed up to 3 years	No
Secondary	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	No
Secondary	Time to progression	Time to event distributions will be estimated using the Kaplan-Meier method.	From registration to disease progression, assessed up to 3 years	No
Secondary	Time to treatment failure	Time to treatment failure will be evaluated using the method of Kaplan-Meier.	From study entry to the date patients end treatment, assessed up to 3 years	No