Treatment Plan for an Individual Patient With Recurrent Uterine Papillary Serous Carcinoma (UPSC) With PIK3CA Gene Mutation

Inclusion Criteria:

1. Patient has adequate bone marrow and coagulation function as shown by: absoluteneutrophil count (ANC) ≥ 1.5 × 109/L; platelets ≥ 100 × 109/L; hemoglobin (Hgb) ≥ 9.0g/dL.

2. Patient has adequate liver function as shown by:

3. total serum bilirubin ≤2.0 mg/dL,

4. ALT and AST ≤2.5x ULN (≤5x ULN in patients with liver metastases),

5. INR ≤2;.

6. Patient has adequate renal function as shown by serum creatinine ≤ 1.5 × ULN.

7. Patient has fasting serum cholesterol ≤ 300mg/dl or 7.75mmol/L AND fastingtriglycerides ≤ 2.5 × ULN. NOTE: In case one or both of these thresholds are exceeded,the patient can only be included after initiation of appropriate lipid loweringmedication.

8. Patient will give a written informed consent obtained according to local guidelines.

9. Sexually active males must use a condom during intercourse while taking everolimus fortreatment, for 8 weeks after stopping treatment, or their female partners should usehighly effective contraception during this specified time period.

10. Women of childbearing potential must have had a negative serum pregnancy test 14 daysprior to the start of everolimus treatment plus a negative local urine pregnancy testprior to treatment and must be willing to use highly effective methods ofcontraception during the study and for 8 weeks after study drug administration.

Exclusion Criteria:

1. Patient has had prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus,deforolimus).

2. Patient has a known intolerance or hypersensitivity to everolimus or other rapamycinanalogs (e.g. sirolimus, temsirolimus).

3. Patient has uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 ×ULN despite adequate therapy. Patients with a known history of impaired fastingglucose or diabetes mellitus (DM) may be included, however blood glucose andantidiabetic treatment must be monitored closely throughout participation in theprogram and adjusted as necessary.

4. Patient has any severe and/or uncontrolled medical conditions such as:

5. unstable angina pectoris, symptomatic congestive heart failure, myocardialinfarction ≤6 months prior to randomization, serious uncontrolled cardiacarrhythmia,

6. active or uncontrolled severe infection,

7. liver disease such as cirrhosis, decompensated liver disease, and chronichepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiableHCV-RNA),

8. known severely impaired lung function (spirometry and DLCO 50% or less of normaland O2 saturation 88% or less at rest on room air),

9. active, bleeding diathesis.

10. Chronic treatment with corticosteroids or other immunosuppressive agents.

11. Patient has a known history of HIV seropositivity.

12. Patient is a woman of child-bearing potential, unless she is using highly effectivecontraception methods.

• Women of child-bearing potential (WOCBP) is defined as all women physiologicallycapable of becoming pregnant, including women whose career, lifestyle, or sexualorientation precludes intercourse with a male partner and women whose partner hasbeen sterilized by vasectomy or other means.

• Highly effective contraception, defined as one that results in an annualpregnancy rate <1% when used correctly, comprises one of the following methods:

• Total abstinence (when this is in line with the preferred and usual lifestyle ofthe subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods ofcontraception)

• Male/female sterilization

• Use of oral, injected or implanted hormonal methods of contraception or placementof an intrauterine device (IUD) or intrauterine system (IUS) or other forms ofhormonal contraception that have comparable efficacy (failure rate <1%), forexample hormone vaginal ring or transdermal hormone contraception

8. Patient is unwilling to or unable to comply with the treatment plan.