Clinical trial NCT01061606: Temsirolimus in Treating Patients With Recurrent or Persistent Cancer of the Uterus
Official title: Pilot Phase II Study of Temsirolimus in Patients With Recurrent Mixed Mesodermal and Mullerian Tumors (Carcinosarcoma) of the Uterus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent Uterine Sarcoma
Uterine Carcinosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-02-03
Enrollment: 8
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Tumor Response Rate, in Terms of the Proportion of Confirmed Tumor Responses (CR or PR) Assessed Using RECIST
timeFrame: Up to 3 years
measure: Progression Free Survival
timeFrame: 6 months from registration
Secondary outcomes:
measure: Overall Survival
timeFrame: From registration to death, assessed up to 3 years
measure: 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
timeFrame: Up to 3 years
measure: Time to Treatment Failure
timeFrame: From study registration to the date patients end treatment, assessed up to 3 years
measure: Time to Progression
timeFrame: Time to progression is defined as the time from registration to disease progression.
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Los Angeles County-USC Medical Center
state: California
city: Pasadena
country: United States
facility: City of Hope Medical Group Inc
state: California
city: Sacramento
country: United States
facility: University of California at Davis Cancer Center
state: California
city: Farmington
country: United States
facility: University of Connecticut
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Paramus
country: United States
facility: The Valley Hospital-Luckow Pavilion
state: New Jersey
city: Albany
country: United States
facility: Women's Cancer Care Associates LLC
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Saint Luke's Roosevelt Hospital Center - Roosevelt Division
state: New York
city: New York
country: United States
facility: Presbyterian-Weill Medical College
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Children's Hospital of New York Presbyterian
state: New York
city: New York
country: United States
facility: Columbia University College of Physicians and Surgeons
state: New York
city: Hershey
country: United States
facility: Penn State Hershey Children's Hospital
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: Montefiore Medical Center - Moses Campus
name: Mark Einstein
role: PRINCIPAL_INVESTIGATOR
References: