Single Arm Trial With Combination of Everolimus and Letrozole in Treatment of Platinum Resistant Relapse or Refractory or Persistent Ovarian Cancer/Endometrial Cancer

This is a single arm, non-randomized, open-label study with a combination of everolimus and
letrozole once a day dosing . Each cycle would be 28days and patients would be scanned after
every 3 cycles for response, until disease progression is documented.

Subjects will take two pills once a day by mouth with a glass of water.

Before the study…

Subjects will need to have the following exams, tests or procedures to find out if they can
be in the study. These exams, tests or procedures are part of regular cancer care and may be
done even if subjects do not join the study. If subjects have had some of them recently,
they may not need to be repeated. This will be up to your study doctor.

- Medical history risk and physical examination,

- Blood tests to measure blood counts, blood mineral levels, and check liver and kidney
function,

- CT scan or MRI of the abdomen and pelvis to measure detectable tumor

- A pregnancy blood test if subjects are capable of becoming pregnant

- Urinalysis (examination of urine)

- The European Organization for research and treatment of cancer global quality of life
questionnaire C30 (QLQ-C30) -This standard questionnaire helps us to measure quality of
life. This questionnaire will take subjects 15 minutes to complete and will be
completed at entry into the study and at week 12 and 24 during the study.

Tests will be done for hepatitis B and/or C if:

- Subjects have a risk of having hepatitis B and/or C or if subjects live or have lived
in specific geographical areas, such as Asia, Africa, Central and South America,
Eastern Europe and Spain, Portugal or Greece;

- The study doctor thinks it is appropriate.

Subjects that have positive hepatitis B or hepatitis C results at screening may be required
to take medication for up to 2 weeks before they start everolimus (Afinitor®) treatment.

During the Study…

If the exams, tests and procedures show that subjects can be in the study, and they choose
to take part, then they will need the following tests and procedures. They are part of
regular cancer care.

- History and physical examination

- Weekly blood tests to measure blood counts, blood mineral levels, blood clotting and
check liver and kidney function

- Evaluation of side effects subjects may experience from the study treatment

- Tests to having hepatitis B and/or C

- CT scan or MRI of the abdomen and pelvis every 12 weeks

- The European Organization for research and treatment of cancer global quality of life
questionnaire C30 (QLQ-C30)

Inclusion Criteria:

- Post-menopausal or post-oophorectomy.

- Performance status Less than or equal to ECOG 2

- Patients must have relapse or refractory or persistent epithelial ovarian, fallopian
tube, primary peritoneal carcinoma or endometrial cancer. Histologic documentation of
the original primary tumor is required via pathology report.

- Patients must have received treatment with a platinum-based chemotherapeutic regimen
for management of primary disease containing carboplatin, cisplatin. This initial
treatment may have included intraperitoneal therapy, consolidation, noncytotoxic
agents (biologic/targeted therapy) or extended therapy administered after surgical or
non-surgical assessment.

- Patients must have platinum-resistant disease, defined as progression < 12 months
after completion of first-or-second-line platinum based chemotherapy. The date
(platinum-free interval) should be calculated from the last administered dose of
platinum therapy.

- Platinum sensitive patients must have progressed/relapsed after receiving a second
line platinum therapy.

- Patients with platinum-refractory primary disease, defined as having disease3
progression while receiving first-line platinum-based chemotherapy.

- Patients are allowed to receive, but are not required to receive, one additional
cytotoxic regimen for management of relapse or refractory or persistent disease.

- Patients are allowed to have received, but are not required to have received,
biologic/targeted therapy (e.g., bevacizumab and/or PARP inhibitor) as part of their
primary treatment regimen or for management of relapse or refractory or persistent
disease.

Exclusion Criteria:

- Patients currently receiving anticancer therapies or who have received anticancer
therapies within 4 weeks of the start of Everolimus (including chemotherapy, antibody
based therapy, etc.); radiation therapy within 2 weeks.

- Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g.

sirolimus, temsirolimus) or to Letrozole.

- Known impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral Everolimus;

- Patients who have any severe and/or uncontrolled medical conditions such as:

1. unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction ≤6 months prior to start of Everolimus, serious uncontrolled cardiac
arrhythmia, or any other clinically significant cardiac disease

2. Symptomatic congestive heart failure of New York heart Association Class III or
IV

3. active (acute or chronic) or uncontrolled severe infection, liver disease such
as cirrhosis, decompensated liver disease, and active or 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;

- Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or
inhaled corticosteroids are allowed;