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

Phase 2
18 Years
Not Enrolling
Recurrent Uterine Sarcoma, Uterine Carcinosarcoma

Thank you

Trial Information

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


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.

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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Tumor response rate, in terms of the proportion of confirmed tumor responses (CR or PR) assessed using RECIST

Outcome Time Frame:

Up to 3 years

Safety Issue:


Principal Investigator

Mark Einstein

Investigator Role:

Principal Investigator

Investigator Affiliation:

Montefiore Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

January 2010

Completion Date:

Related Keywords:

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



Montefiore Medical Center Bronx, New York  10467-2490