Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer
Condition: Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Carcinoma, Endometrioid; Cystadenocarcinoma; Cystadenocarcinoma, Serous; Adenocarcinoma, Papillary; Recurrence
Intervention: Everolimus; Laboratory Biomarker Analysis; Letrozole
Intervention description: Given PO; Correlative studies; Given PO
Intervention MeSH terms: Everolimus; Letrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This pilot, phase II trial studies how well everolimus and letrozole work in treating
      patients with hormone receptor positive ovarian, fallopian tube, or primary peritoneal cavity
      cancer that has come back. Everolimus and letrozole may stop the growth of tumor cells by
      blocking some the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed estrogen receptor positive (greater than 10%) recurrent
             ovarian, fallopian tube or primary peritoneal carcinoma in post-menopausal women;
             note: pure clear cell and pure mucinous carcinomas are ineligible; both platinum
             sensitive, platinum resistant and platinum refractory disease are eligible; no
             limitations in the number of prior regimens

          -  Patient has disease amenable to biopsy and is agreeable to undergo a biopsy; note:
             under unusual circumstances, submission of ascites material may be acceptable if a
             biopsy is not possible; this will require approval by one of the study principal
             investigators

          -  Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin > 9.0 g/dL

          -  Total serum bilirubin =< 2 mg/dL

          -  Aspartate transaminase (AST) =< 2.5 x upper limit of normal (ULN) (=< 5 x ULN in
             patients with liver metastasis)

          -  International normalized ratio (INR) =< 2

          -  Creatinine =< 1.5 x ULN

          -  Fasting serum cholesterol =< 300 mg/dL or =< 7.75 mmol/L and fasting triglycerides =<
             2.5 x ULN; in case of any of these thresholds be exceeded, the patient can only be
             included after initiation of appropriate lipid lowering medications

          -  Provide informed written consent

          -  Willing to return to enrolling institution for follow-up (during the active monitoring
             phase of the study)

          -  Willing to provide tissue samples for correlative research purposes

        Exclusion Criteria:

          -  Any of the following

               -  Pregnant women

               -  Nursing women

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens including but not limited to any of the following that would limit
             compliance with study requirements:

               -  Ongoing or active severe infection

               -  Liver disease such as cirrhosis

               -  Decompensated liver disease

               -  Symptomatic congestive heart failure (New York heart Association class III or IV)

               -  Unstable angina pectoris, serious uncontrolled cardiac arrhythmia, myocardial
                  infarction =< 6 months prior to registration

               -  Known severely impaired lung function (spirometry and diffusing capacity of the
                  lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation
                  88% or less at rest on room air)

               -  Active bleeding diathesis

               -  Psychiatric illness

          -  Known to be human immunodeficiency virus (HIV) positive

          -  Receiving any other investigational agent =< 4 weeks prior to registration which would
             be considered as treatment for the primary neoplasm

          -  Other active malignancy =< 3 years prior to registration; exceptions: non-melanotic
             skin cancer or carcinoma-in-situ of the cervix, uterus or breast; note: if there is a
             history of prior malignancy, they must not be receiving other specific treatment for
             their cancer

          -  Patients currently receiving anticancer therapies or who have received anticancer
             therapies =< 4 weeks prior to registration (including chemotherapy, radiation therapy,
             antibody based therapy, etc.)

          -  Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g.
             sirolimus, temsirolimus)

          -  Known impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of oral everolimus

          -  Uncontrolled diabetes mellitus as defined by hemoglobin (Hb)A1c > 8% despite adequate
             therapy; note: patients with a known history of impaired fasting glucose or diabetes
             mellitus (DM) may be included, however blood glucose and antidiabetic treatment must
             be monitored closely throughout the trial and adjusted as necessary

          -  Chronic treatment with corticosteroids or other immunosuppressive agents; note:
             topical or inhaled corticosteroids are allowed

          -  Patients who have received live attenuated vaccines =< 1 week prior to registration
             and during the study; note: patient should also avoid close contact with others who
             have received live attenuated vaccines; examples of live attenuated vaccines include
             intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin
             (BCG), yellow fever, varicella and TY21a typhoid vaccines

          -  History of non-compliance to medical regimens or who are considered potentially
             unreliable or will not be able to complete the entire study

          -  Prior therapy with everolimus or an aromatase inhibitor

          -  Known brain metastasis

          -  Active and chronic viral hepatitis (i.e. quantifiable serum hepatitis B virus
             [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B virus surface antigen
             [HBsAg], or quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA] in serum)