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

The objective is to provide access to everolimus for patients with Recurrent UPSC and limited
treatment alternatives.

Letrozole 2.5mg daily q 30 days Everolimus 10mg daily q 28 days

Inclusion Criteria:

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

2. Patient has adequate liver function as shown by:

1. total serum bilirubin ≤2.0 mg/dL,

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

3. INR ≤2;.

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

4. Patient has fasting serum cholesterol ≤ 300mg/dl or 7.75mmol/L AND fasting
triglycerides ≤ 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 lowering
medication.

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

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

7. Women of childbearing potential must have had a negative serum pregnancy test 14 days
prior to the start of everolimus treatment plus a negative local urine pregnancy test
prior to treatment and must be willing to use highly effective methods of
contraception 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 rapamycin
analogs (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 fasting
glucose or diabetes mellitus (DM) may be included, however blood glucose and
antidiabetic treatment must be monitored closely throughout participation in the
program and adjusted as necessary.

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

1. unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction ≤6 months prior to randomization, serious uncontrolled cardiac
arrhythmia,

2. active or uncontrolled severe infection,

3. liver disease such as cirrhosis, decompensated liver disease, and chronic
hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable
HCV-RNA),

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

5. active, bleeding diathesis.

5. Chronic treatment with corticosteroids or other immunosuppressive agents.

6. Patient has a known history of HIV seropositivity.

7. Patient is a woman of child-bearing potential, unless she is using highly effective
contraception methods.

- Women of child-bearing potential (WOCBP) is defined as all women physiologically
capable of becoming pregnant, including women whose career, lifestyle, or sexual
orientation precludes intercourse with a male partner and women whose partner has
been sterilized by vasectomy or other means.

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

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

- Male/female sterilization

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

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