A Pilot Study of Induction Wee1 Inhibition in Ovarian Cancer

Study Drug Administration:

A study cycle is 28 days.

If you are found to be eligible to take part in this study, you will begin taking AZD1775 on
the day of your laparoscopy. You will first take AZD1775 capsules 1 time each day on Days
1-5. Depending on when your tumor reduction surgery is scheduled, you may continue taking the
study drug on Days 8-12, 15-19, and 22-26. The study doctor will discuss this with you.

Before every time you take AZD1775 capsules, you will take ondansetron (Zofran). Before your
first dose of AZD1775 each week, you will take dexamethasone. You may also receive
dexamethasone before additional doses of AZD1775. Ondansetron and dexamethasone are standard
drugs given 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.

Your daily dose of AZD1775 should be taken about 2 hours before or after eating. If you vomit
after taking your dose of AZD1775, you should not retake the dose. Wait until your next
scheduled dose.

Your dose of AZD1775 on Day 1 should be taken at least 1 hour after your laparoscopy.

You will need to record when you take each dose in a study drug diary. The study staff will
give you the study drug diary and show you how to fill it out.

You will stop taking AZD1775 capsules about 1-4 days before your tumor reduction surgery.
After you have recovered from surgery (about 3-6 weeks later), you will receive standard
chemotherapy treatment. The chemotherapy is part of your standard of care treatment and is
not part of this research study. The type of chemotherapy you receive will be up to your
doctor.

Study Visits:

On the day of your laparoscopy:

- You will have a physical exam.

- Blood (about 1-2 teaspoons) will be drawn for routine tests.

- Tumor tissue will be collected during your laparoscopy procedure for biomarker and
genetic testing. All samples will be stored at the MD Anderson Gynecologic Oncology
Tumor Bank for an unlimited amount of time for testing related to this study. Your
samples will be given a code number. No identifying information will be directly linked
to your samples. Only the researcher in charge of the bank will have access to the code
numbers and be able to link the samples to you. This is to allow medical data related to
the samples to be updated as needed.

While you are taking the AZD1775, you will have weekly visits. At each visit:

- You will have a physical exam.

- Blood (about 2-3 tablespoons) will be drawn for routine and biomarker testing.

If you do not have tumor reduction surgery, you will stop having study visits after your last
dose of AZD1775 and continue on to the follow-up part of the study (described below). If you
do go on to have tumor reduction surgery, you will have the below study visits.

You will be asked to sign a separate consent document for your tumor reduction surgery that
will explain the procedure and its risks.

On the day of your pre-operative visit:

- You will have a physical exam.

- Blood (about 2-3 tablespoons) will be drawn for routine, genetic, and biomarker testing.

- You will have an EKG.

On the day of your surgery:

- Tumor tissue will be collected for genetic and biomarker testing during your already
scheduled tumor reduction surgery. All samples will be stored at the MD Anderson
Gynecologic Oncology Tumor Bank for an unlimited amount of time for testing related to
this study.

- Blood (about 1-2 teaspoons) will be drawn for routine tests.

On the day of your post-operative visit:

- You will have a physical exam.

- Blood (about 1-2 teaspoons) will be drawn for routine and biomarker testing.

- If the doctor thinks it is needed, you will have an EKG.

Length of Treatment:

You may take the study drug up to 26 days (including the rest days in between your doses).
You will no longer be able to take the study drug if intolerable side effects occur, you are
not eligible for treatment or surgery, or you are unable to follow study directions.

Your participation on this study will be over after follow-up.

Follow-Up:

Within 30 days after your surgery:

- You will have a physical exam.

- Blood (about 2-3 tablespoons) will be drawn for routine, genetic, and biomarker testing.

- If the doctor thinks it is needed, you will have an EKG.

Standard Follow-Up:

You will continue to have follow-up visits every 3 months as part of your standard care.

Inclusion Criteria:

1. Patients with presumed advanced-stage high grade serous ovarian, fallopian tube, or
primary peritoneal carcinoma, based on the presence of carcinomatosis, and/or elevated
CA125, and/or ovarian mass(es), or at the discretion of the treating physician.

2. Medically able to undergo primary cytoreductive surgery, at least 13 days and up to 28
days after starting study drug, as determined by treating physician.

3. No prior therapy for high-grade serous ovarian, fallopian tube, or primary peritoneal
carcinoma.

4. Patients must be able to swallow and tolerate oral medications and not have
gastrointestinal illnesses that would preclude absorption of AZD1775 (e.g.
uncontrolled nausea, vomiting, or diarrhea; malabsorption syndrome; ulcerative
disease). Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube
or be receiving total parenteral nutrition (TPN).

5. Patients must have normal organ and marrow function (measured within 7 days prior to
the initiation of therapy) as defined below: a. Absolute neutrophil count >/=
1,500/mcL; b. Hemoglobin >/= 9gm/dL; c. Platelets >/= 100,000/mcL; d. Total Bilirubin
involved with tumor, in that case, AST and ALT must be f. Creatinine clearance > 50 mL/min (assessed by Cockcroft Gault estimation) and
creatinine < 1.5 x ULN.

6. Patients must have an ECOG performance status of 0 or 1.

7. Women of childbearing potential (WoCBP) may be included only if acceptable
contraception is in place for two weeks before study entry, for the duration of the
study and for 90 days after the last dose of AZD1775. WoCBP are defined as those who
are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or
complete hysterectomy) or postmenopausal (defined as 12 months with no menses without
an alternative medical cause). Acceptable methods of contraception include true
abstinence in line with the preferred and usual lifestyle choice of the patient, tubal
ligation, vasectomised partner, barrier methods (eg, cap plus spermicide, sponge plus
spermicide, diaphragm plus spermicide, or male condom plus a spermicide), intrauterine
device methods (eg, Copper T or Levonorgestrel-releasing intrauterine system), or
hormonal methods (eg, any registered and marketed contraceptive agent that contains an
oestrogen and/or a progestational agent

8. (Continued from previous criterion) and that is administered via the oral,
subcutaneous, transdermal, intrauterine, or intramuscular route as an implant, hormone
shot or injection, combined pill, minipill or patch. All methods of contraception
(with the exception of total abstinence) should be used in combination with the use of
a condom by their male sexual partner for intercourse. Periodic abstinence, the rhythm
method, and the withdrawal method are not acceptable methods of birth control. All
WoCBP must have a negative pregnancy test within 3 days prior to study the initiation
of therapy.. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.

9. It is unknown if AZD1775 will be present in human breast milk. For this reason, women
must not breast-feed while taking the study medications.

10. Patients must be able to understand and willing to sign an informed consent.

11. Patients must be at least 18 years of age.

Exclusion Criteria:

1. Prior treatment for ovarian, fallopian tube, or primary peritoneal cancer

2. Current receipt of any other investigational agents or any additional anti-cancer
agents for this or any other disease

3. Known central nervous system (CNS) disease other than neurologically stable, treated
brain metastases -- defined as metastasis having no evidence of progression or
haemorrhage after treatment for at least 2 weeks

4. Presence of other active cancers. Patients with Stage I cancer who have received
definitive local treatment within the last 3 years, and whom are considered unlikely
to recur, are eligible. All patients with previously treated in-situ carcinoma (i.e.,
non-invasive) are eligible, as are patients with prior non-melanoma skin cancers.

5. Major surgical procedures procedures waiting required following port-a-cath placement.

6. Significant symptom burden from presumed diagnosis including large volume ascites,
pain requiring narcotic medication, or shortness of breath on exertion

7. Myocardial infarction within 6 months before starting therapy, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or unstable
cardiac arrhythmia requiring medication

8. Corrected QT interval (QTc) >470 msec (as calculated by Fridericia correction formula)
at study entry or congenital long QT syndrome

9. Caution should be exercised when inhibitors or substrates of P-gP, substrates of
CYP1A2 with a narrow therapeutic range, sensitive substrates of CYP2C19 or CYP2C19
substrates with a narrow therapeutic range are administered with AZD1775.

10. Herbal preparations are not allowed throughout the study. These herbal medications
include, but are not limited to: St. John's wort, kava, ephedra (ma huang), gingko
biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Not willing
to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos,
and exotic citrus fruits from 14 days prior to the dose of study medication and during
the entire study due to potential CYP3A4 interaction with the study medication. Orange
juice is allowed.

11. Any known hypersensitivity or contraindication to the components of study treatment

12. Pregnant or breast-feeding

13. As judged by the Investigator, any evidence of severe or uncontrolled systemic
diseases (e.g., severe hepatic impairment, interstitial lung disease [bilateral,
diffuse, parenchymal lung disease], uncontrolled chronic renal diseases
[glomerulonephritis, nephritic syndrome, Fanconi Syndrome or Renal tubular acidosis]),
serious active infection or current unstable or uncompensated respiratory or cardiac
conditions, or uncontrolled hypertension (blood pressure >/= 140/90), active bleeding
diatheses or active infection including hepatitis B, hepatitis C, and human
immunodeficiency virus. Screening for chronic conditions and infectious diseases is
not required.

14. As judged by the Investigator, the patient is unsuitable to participate in the study
and the patient is unlikely to comply with study procedures, restrictions, and
requirements.

15. Subject has had prescription or non-prescription drugs or other products known to be
sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or
to be moderate to strong inhibitors / inducers of CYP3A4 which cannot be discontinued
two weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks
after the last dose of study drug. Co-administration of aprepitant or fosaprepitant
during this study is prohibited.

16. AZD1775 is an inhibitor of breast cancer resistance protein (BCRP). The use of statins
including Atorvastatin which are substrates for BCRP are therefore prohibited and
patients should be moved on to non-BCRP alternatives.