Dose-Escalation Study of Intraperitoneal (IP) Cisplatin, IV/IP Paclitaxel, IV Bevacizumab, and Oral Olaparib for Newly Diagnosed Ovarian, Primary Peritoneal, and Fallopian Tube Cancer

Patients with synchronous primary endometrial cancer or a past history of endometrial cancer, unless all of the following conditions are met:

Stage not greater than IB

No more than superficial myometrial invasion

No vascular or lymphatic invasion

No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO Grade 3 lesions.

Subjects who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded. Prior intravaginal brachytherapy is permitted. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than 3 years prior to enrollment, and the subject remains free of recurrent or metastatic disease.

Patients who have received prior chemotherapy for any abdominal or pelvic tumor are excluded. Patients who have received neoadjuvant chemotherapy prior to their initial debulking are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer.

With the exception of non-melanoma skin cancer and other specific malignancies as noted above, subjects with other invasive malignancies who had (or have) any evidence of the other cancer present within the last 3 years or whose previous cancer treatment contraindicates this protocol therapy are excluded.

Patients who have received prior bevacizumab (or any other VEGF targeted agent) or prior PARP inhibitor.

Subjects with acute hepatitis.

Subjects with active infection that requires parenteral antibiotics.

\> Grade 1 hearing loss or tinnitus

Patients who are pregnant or nursing.

Patients under the age of 18.

Patients with clinical symptoms or signs of gastrointestinal obstruction, require parenteral hydration or nutrition, require a drainage gastrostomy tube and/or have any other impairment that limits their ability to take oral medication.

Patients with serious non-healing wound, ulcer, or bone fracture including history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days. Patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations.

Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.

Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study.

Patients with clinically significant cardiovascular disease including

Uncontrolled hypertension, defined as systolic \> 150 mm Hg or diastolic \> 90 mm Hg.

Myocardial infarction or unstable angina \< 6 months prior to registration.

New York Heart Association (NYHA) Class II or higher congestive heart failure

Serious cardiac arrhythmia requiring medication.

CTEP CTCAE Version 4.0, Grade 2 or higher peripheral ischemia \[brief (\<24 hrs) episode of ischemia managed non-surgically and without permanent deficit\].

Core biopsy or other minor surgical procedure (excluding placement of a vascular access device, paracentesis, and/or thoracentesis) within 7 days prior to the first date of bevacizumab therapy.

Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.

Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4. Lists including medications or substances known or with the potential to interact with these enzymes.

What this study is about