Temsirolimus in Treating Patients With Metastatic or Locally Advanced Recurrent Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma
MeSH terms: Carcinoma; Endometrial Neoplasms; Adenomyoepithelioma; Adenocarcinoma, Clear Cell; Cystadenocarcinoma, Serous; Carcinoma, Adenosquamous; Recurrence
Intervention: temsirolimus; laboratory biomarker analysis
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well temsirolimus works in treating patients with endometrial
      cancer that has spread to other parts of the body or has spread from where it started to
      nearby tissue or lymph nodes and has come back after a period of time during which the cancer
      could not be detected. Temsirolimus may stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed metastatic and/or locally advanced
             recurrent adenocarcinoma (papillary serous, papillary, villoglandular, mucinous, clear
             cell), endometrioid or adenosquamous carcinoma of the endometrium, incurable by
             standard therapies

          -  Patients must have tumour tissue from their primary tumor available to assess
             molecular markers of CCI-779 activation (paraffin block or unstained slides)

          -  Presence of clinically and/or radiologically documented disease; at least one site of
             disease must be unidimensionally measurable as follows:

               -  X-ray, physical exam >= 20 mm

               -  Spiral computed tomography (CT) scan >= 10 mm

               -  Non-spiral CT scan >= 20 mm

               -  All radiology studies must be performed within 28 days prior to registration
                  (within 35 days if negative)

          -  Patients must have a life expectancy of at least 12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2

          -  Previous therapy:

               -  Hormonal therapy:

                    -  Group A: One prior hormonal treatment (progestational or aromatase
                       inhibitor) as either adjuvant therapy or for treatment of metastatic disease

                    -  Group B: No limit to number of prior hormonal treatments given
                       (progestational or aromatase inhibitor) as either adjuvant therapy or for
                       treatment of metastatic disease

                    -  Time since last hormone: >= 1 week since last dose of hormonal therapy
                       (applies to both Groups)

               -  Chemotherapy:

                    -  Group A: No prior chemotherapy

                    -  Group B: Patients must have had one prior regimen of chemotherapy for
                       metastatic disease; patients must be 4 weeks since last dose of chemotherapy

               -  Radiation: Patients may have had prior radiation therapy; a minimum of 28 days
                  must have elapsed between the end of radiotherapy and registration onto the
                  study; (exceptions may be made however, for low dose, palliative radiotherapy;
                  patients must have recovered from any acute toxic effects from radiation prior to
                  registration

               -  Previous surgery: Previous major surgery is permitted provided that it has been
                  at least 21 days prior to patient registration and that wound healing has
                  occurred

          -  Granulocytes (absolute granulocyte count [AGC]) >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Bilirubin =< upper normal limit (UNL)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x UNL

          -  Serum creatinine =< 1.5 x UNL or creatinine clearance >= 50 ml/min; creatinine
             clearance to be measured directly by 24 hour urine sampling or as calculated by
             Cockcroft Formula

          -  Fasting serum cholesterol =< 9.0 mmol/L

          -  Fasting triglycerides =< 4.56 mmol/L

          -  Patient consent must be obtained according to local Institutional and/or University
             Human Experimentation Committee requirements; it will be the responsibility of the
             local participating investigators to obtain the necessary local clearance, and to
             indicate in writing to the National Cancer Institute of Canada Clinical Trials Group
             (NCIC CTG) Study Coordinator that such clearance has been obtained, before the trial
             can commence in that centre; because of differing requirements, a standard consent
             form for the trial will not be provided but a sample form is given; a copy of the
             initial full board Research Ethics Board (REB) approval and approved consent form must
             be sent to the central office; the patient must sign the consent form prior to
             randomization or registration; please note that the consent form for this study must
             contain a statement which gives permission for the NCIC CTG and monitoring agencies to
             review patient records

          -  Patients must be accessible for treatment and follow-up; patients registered on this
             trial must be treated and followed at the participating center; this implies there
             must be reasonable geographical limits (for example: 1 ½ hour's driving distance)
             placed on patients being considered for this trial; investigators must assure
             themselves the patients registered on this trial will be available for complete
             documentation of the treatment, adverse events, response assessment and follow-up

          -  In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working
             days of patient registration

        Exclusion Criteria:

          -  Patients with a history of other malignancies, except: adequately treated non-melanoma
             skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors
             curatively treated with no evidence of disease for >= 5 years

          -  Patients must not have had prior treatment with an mammalian target of rapamycin
             (mTOR) inhibitor

          -  Uterine sarcomas (leiomyosarcoma), mixed mullerian tumours (MMT) and/or adenosarcomas

          -  Patients with non-measurable disease only; (please note that bone metastases are
             considered non-measurable)

          -  Pregnant or lactating women; pregnant women are excluded from this study;
             breastfeeding should be discontinued if the mother is treated with CCI-779; most
             patients enrolled on this trial will have had a prior hysterectomy or pelvic
             irradiation; however, if the patient is of childbearing potential, a urine beta-human
             chorionic gonadotropin (HCG) must be proved negative within 7 days prior to
             registration; women of child-bearing potential must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation; should a woman become pregnant or
             suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately

          -  Patients with known brain metastases; (a head CT is not necessary to rule out brain
             metastases, unless there is clinical suspicion of central nervous system [CNS]
             involvement)

          -  Patients with serious cardiovascular illness such as myocardial infarction within 6
             months prior to entry, congestive heart failure (even if medically controlled),
             unstable angina, active cardiomyopathy, unstable ventricular arrhythmia or
             uncontrolled hypertension

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to CCI-779

          -  Patients receiving concurrent treatment with other anti-cancer therapy or other
             investigational agents

          -  Serious illness or medical condition which would not permit the patient to be managed
             according to the protocol including, but not limited to:

               -  History of significant neurologic or psychiatric disorder which would impair the
                  ability to obtain consent or limit compliance with study requirements

               -  Active uncontrolled infection

               -  Active peptic ulcer disease

               -  Any other medical conditions that might be aggravated by treatment