Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer
Condition: Endometrial Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC1 Uterine Corpus Cancer; Stage IIIC2 Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer
MeSH terms: Carcinoma; Endometrial Neoplasms; Recurrence
Intervention: Laboratory Biomarker Analysis; Megestrol Acetate; Tamoxifen Citrate; Temsirolimus
Intervention description: Correlative studies; Given PO; Given PO; Given IV
Intervention MeSH terms: Tamoxifen; Sirolimus; Temsirolimus; Megestrol; Megestrol Acetate; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 73.0
Sex: Female
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well temsirolimus with or without megestrol
      acetate and tamoxifen citrate works in treating patients with endometrial cancer that has
      spread to other places in the body and usually cannot be cured or controlled with treatment,
      has returned after a period of improvement, or is persistent. Temsirolimus may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can
      cause the growth of endometrial cancer cells. Hormone therapy using megestrol acetate and
      tamoxifen citrate may fight endometrial cancer by blocking the use of estrogen by the tumor
      cells. It is not yet known whether temsirolimus is more effective when given alone or
      together with megestrol acetate and tamoxifen citrate in treating endometrial cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed advanced (International Federation of
             Gynecologists and Obstetricians [FIGO] stage III or IV), persistent, or recurrent
             endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy;
             histologic documentation of the recurrence is not required

          -  All patients must have measurable disease; measurable disease is defined as at least
             one lesion that can be accurately measured in at least one dimension (longest
             dimension to be recorded); each lesion must be >= 20 mm when measured by conventional
             techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic
             resonance imaging (MRI), or >= 10 mm when measured by spiral CT

          -  Patients must have at least one "target lesion" to be used to assess response, as
             defined by Response Evaluation Criteria In Solid Tumors (RECIST); tumors within a
             previously irradiated field will be designated as "non-target" lesions unless
             progression is documented

          -  Prior chemoradiotherapy for a pelvic recurrence is permitted; prior chemotherapy in
             the adjuvant setting for stage I, II, or III disease is permitted

               -  Note: no prior chemotherapy in the setting of stage IV disease is permitted
                  unless the patient was without evidence of disease at the completion of
                  chemotherapy and had at least six months of progression-free survival since the
                  completion of chemotherapy

               -  Regardless of circumstances, no more than one prior chemotherapy regimen
                  (including chemoradiotherapy) is permitted

          -  Patient must be able to take p.o. medications

          -  Performance status must be 0-2

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =<
             2.5 times institutional upper limit of normal v 3.0 (=< 5 times upper limit of normal
             [ULN] for subjects with liver metastases)

          -  Alkaline phosphatase =< 2.5 times institutional upper limit of normal v 3.0 (=< 5
             times ULN for subjects with liver metastases)

          -  Creatinine =< 1.5 times normal institutional upper limit of normal

          -  Cholesterol =< 350 mg/dL (fasting)

          -  Triglycerides =< 400 mg/dL (fasting)

          -  Albumin >= 3.0 mg/dL

          -  At least 4 weeks must have elapsed since the patient underwent any major surgery
             (e.g., major: hysterectomy, resection of a lung nodule-minor: a Port-A-Cath placement)

          -  Patients who have met the pre-entry requirements

          -  Patients must have signed an approved informed consent including Health Insurance
             Portability and Accountability Act (HIPAA) authorization

        Exclusion Criteria:

          -  Patients with Gynecologic Oncology Group (GOG) performance status of 3 or 4

          -  Patients cannot be receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g.,
             phenytoin, carbamazepine, phenobarbital) nor any other cytochrome P450, family 3,
             subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's wort, as
             these may decrease temsirolimus levels; use of agents that potently inhibit CYP3A (and
             hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not
             specifically prohibited; the appropriateness of use of such agents is left to
             physician discretion

               -  All concomitant medications must be recorded at baseline

          -  Patients on maintenance corticosteroids are ineligible with the exception of short
             term use (fewer than 5 days)

          -  Patients known to have congestive heart failure; patients with baseline requirement
             for oxygen; patients with serious concomitant illness that, in the opinion of the
             treating physician, will place patient at unreasonable risk from therapy on this
             protocol

          -  Patients with a history of unprovoked deep vein thrombosis (DVT) or pulmonary embolism
             (PE), unless patient is maintained on anticoagulation for the duration of the trial;
             while the exact definition of "provoked" is left to the treating physician, a DVT in
             the setting of pelvic surgery or trauma would be considered "provoked"

          -  Women of child-bearing potential must have a negative pregnancy test prior to
             treatment on study; breastfeeding should be discontinued if the mother is treated with
             temsirolimus

               -  Women of child-bearing potential and men must agree to use adequate contraception
                  (barrier method of birth control or abstinence; oral contraceptives [also known
                  as "the pill"] are not acceptable) 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 a concomitant invasive malignancy or a history of other invasive
             malignancies, with the exception of non-melanoma skin cancer, are excluded if there is
             any evidence of other malignancy being present within the past five years; patients
             are also excluded if their previous cancer treatment contraindicates this protocol
             therapy

          -  Patients who have received hormonal therapy or biologic therapy as treatment for
             endometrial carcinoma

          -  Patients who have received chemotherapy directed at metastatic or recurrent
             endometrial carcinoma