Fulvestrant Plus Palbociclib in Women With Advanced Low Grade Serous Carcinoma

Study Drug Administration:

Every study cycle will be 28 days. You will receive treatment in 2 periods: Neoadjuvant
Treatment (before surgery) and Adjuvant Treatment (after surgery).

Neoadjuvant Treatment (Cycles 1-4):

There are 4 cycles in the neoadjuvant treatment period. On Days 1 and 15 of Cycle 1 and Day 1
of Cycles 2-4, you will receive fulvestrant as an injection in your buttocks. On Days 1-21 of
each cycle, you will take palbociclib tablets by mouth at about the same time each day,
preferably with food. You will not take palbociclib during Days 22-28.

Palbociclib should be swallowed whole; not chewed. If a capsule is broken, cracked, or
otherwise not whole, do not take it.

Surgery:

After 4 cycles of neoadjuvant treatment, you will have your scheduled surgery as part of your
standard care. You will sign a separate consent for this surgery describing the procedure and
its risks in more detail.

Adjuvant Treatment (Cycles 5 and beyond):

After you have recovered from surgery (about 3-6 weeks later), you will begin receiving
fulvestrant and palbociclib. On Day 1 of each cycle, you will receive fulvestrant as an
injection in your buttocks. On Days 1-21 of each cycle, you will take palbociclib tablets by
mouth. You will not take palbociclib during Days 22-28.

You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

Length of Study:

You will receive the study drug(s) for as long as the study doctor thinks it is in your best
interest. You will no longer be able to take the study drugs if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Your participation in this study will be over after the 30-day follow-up phone call
(described below).

Study Visits:

On Day 1 of each cycle:

- You will have a physical exam. If the study doctor thinks it is needed, you will also
have a pelvic exam.

- Blood (about 4 tablespoons) will be drawn for routine, tumor marker, and biomarker
tests.

- Urine will be collected for routine tests.

- You will have an EKG.

- If you can become pregnant, urine will be collected and/or part of this blood sample
will be used for a pregnancy test.

On Day 15 of Cycle 1, you will have a physical exam.

On Day 1 of odd-numbered cycles after Cycle 1 (Cycles 3, 5, 7, and so on), you will have an
MRI or CT scan.

At your visit before the surgery, you will have a CT scan or MRI to check the status of the
disease.

During surgery, some of the tissue removed will be used to compare to tissue collected from
you before you received chemotherapy so researchers can learn if the study drugs had any
affect on the disease. This sample will be stored at MD Anderson for an unlimited amount of
time for testing related to this study.

End-of-Treatment Visit:

After the last dose of study drug(s):

- You will have a physical exam.

- Blood (about 1-2 tablespoons) will be drawn for routine, tumor marker, and biomarker
tests.

- You will have an MRI or CT scan to check the status of the disease.

Follow-Up:

About 30 days after the last dose of study drugs, the study staff will call you and ask how
you are doing. This call should last about 5 minutes.

Inclusion Criteria:

1. Patients with clinical or surgical stage III or IV low-grade serous ovarian, primary
peritoneal, or fallopian tube carcinomas who in the judgement of the treating
physician are unlikely to achieve optimal surgical cytoreduction and have been
recommended to receive neoadjuvant therapy.

2. Histological diagnosis must be based on surgical or core biopsy not just fine needle
aspiration. Biopsies performed at other institutions must undergo pathology review and
confirmation at MD Anderson Cancer Center.

3. Tissue from an archival tissue sample or fresh tissue obtained from a core or
excisional biopsy of a tumor lesion.

4. Willingness to provide pre- and post-treatment tissue for translational studies.
Pre-treatment fresh frozen tissue must be available for research purposes. This tissue
can be collected from preoperative laparoscopy, other diagnostic biopsy, or a
research-specific biopsy.

5. Signed informed consent on protocol LAB02-188.

6. Tissue from an archival tissue sample or fresh tissue obtained from a core or
excisional biopsy of a tumor lesion.

7. Patients whose clinical biopsies are found to be insufficient for the planned
translational studies must be willing to undergo a research biopsy.

8. Patients must have measurable disease by RECIST v1.1. a. Measurable disease is defined
at least one lesion that can be accurately measured in at least one dimension (longest
dimension to be recorded). Each target lesion must be >20 mm when measured by
conventional techniques, including palpation, plain x-ray, CT, and MRI, or >10 mm when
measured by spiral CT.

9. Women 18 years of age or older.

10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

11. Abnormal organ function is permitted. However, patients must have: a. absolute
neutrophil count >/= 1500/mL b. platelets >/= 100,000/mL c. hemoglobin >/= 9 g/dL d.
estimated creatinine clearance >/= 60 ml/min as calculated using the method standard
for the institution e. total serum bilirubin aminotransferase (AST/SGOT) and/or alanine aminotransferase (ALT/SGPT) (
12. Resolution of all acute toxic effects of prior therapy or surgical procedures to
National Cancer Institute (NCI) CTCAE 4.03 Grade
13. Women of child-bearing potential (intact uterus) MUST have a negative serum or urine
human chorionic gonadotropin (HCG) test within 72 hours prior to receiving the first
dose of study medication. Patients of childbearing potential are those who have not
been surgically sterilized or have not been free from menses for > 1 year. If the
urine test is positive or cannot be confirmed as negative, a serum pregnancy test will
be required.

14. Female patients of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 120 days after the last dose of study medication (Reference
Section 7.7). Patients of childbearing potential are those who have not been
surgically sterilized or have not been free from menses for > 1 year. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately

15. Pre/perimenopausal women must be amenable to be treated with goserelin. All patients
will be rendered post-menopausal secondary to concomitant administration of goserelin.

16. Ability to understand and willingness to sign informed consent form prior to
initiation of the study and any study procedures.

Exclusion Criteria:

1. Patients who are pregnant or breastfeeding.

2. Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be
potent CYP3A4 inducers (for examples, see the Prohibited Concomitant Medications
section), and drugs that are known to prolong the QT interval (see Prohibited
Concomitant Medications in section 7.6.2).

3. QTc interval >480 msec (based on the mean value of the triplicate ECGs), family or
personal history of long or short QT syndrome, Brugada syndrome or known history of
QTc prolongation or Torsade de Pointes.

4. Diagnosis of another malignancy within 3 years, except for adequately treated basal
cell or squamous cell skin cancer, or carcinoma in situ of the cervix.

5. Previous chemotherapy or hormonal therapy for treatment of ovarian cancer.

6. Known Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) infection.

7. Inability or unwillingness to swallow pills.

8. Active infection requiring intravenous (IV) antibiotics or other uncontrolled
intercurrent illness requiring hospitalization.

9. Impairment of gastro-intestinal (GI) function or GI disease that may significantly
alter the absorption of palbociclib, such as history of GI surgery which may result in
intestinal blind loops and patients with clinically significant gastroparesis, short
bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or
diarrhea of CTCAE Grade >1.

10. Inability to comply with the study and follow-up procedures.

11. Any of the following: myocardial infarction, severe/unstable angina, ongoing cardiac
dysrhythmias of NCI CTCAE Grade >/= 2, atrial fibrillation of any grade,
coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
cerebrovascular accident including transient ischemic attack, uncontrolled seizures or
brain metastases or pulmonary embolism.

12. Prior hematopoietic stem cell or bone marrow transplantation.

13. Known abnormalities in coagulation such as bleeding diathesis, or treatment with
anticoagulants precluding intramuscular injections of fulvestrant or goserelin (if
applicable).

14. Known or possible hypersensitivity to fulvestrant, or palbociclib or any of their
excipients.

15. Pre/perimenopausal women with a known hypersensitivity to gnRH