Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer

PRIMARY OBJECTIVES:

I. To determine whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy
(HIPEC) followed by postoperative normothermic intraperitoneal (IP) chemotherapy is feasible
and safe to administer, as measured by toxicities occurring during treatment or follow-up.

SECONDARY OBJECTIVES:

I. To determine quality of life (QoL) and compare the outcomes to a historical control of IP
chemotherapy (no HIPEC) for women with ovarian cancer.

II. To determine whether cytoreductive surgery with HIPEC alone is feasible and safe to
administer, as measured by toxicities occurring during treatment or follow-up.

III. To estimate progression-free survival (PFS).

IV. To collect biospecimens and perform correlative translational studies focused on
understanding the mechanisms of action of HIPEC on ovarian cancer and micro ribonucleic acid
(RNA) profiling of ovarian cancer and ex vivo evaluation of oncolytic virus replication.

OUTLINE: Patients undergo surgery and receive hyperthermic cisplatin intraperitoneally (IP)
over 60 minutes. Beginning at least 3 weeks after surgery, patients may receive carboplatin,
paclitaxel, pegylated liposomal doxorubicin hydrochloride, or gemcitabine hydrochloride IP or
intravenously (IV) at the discretion of the medical and gynecologic oncologists.

After completion of study treatment, patients are followed up at 3-6, 6-9, 9-12, and 12-15
months; every 3 months for 1 year; and then every 4 months for 1 year.

Inclusion Criteria:

- Provided informed consent

- Patient with primary or recurrent International Federation of Gynecology and
Obstetrics (FIGO) stage III or IV ovarian, fallopian tube, peritoneal carcinoma, or
uterine cancer, confined to abdominal cavity, including those who have completed
neoadjuvant chemotherapy and primary surgery

- Gynecologic Oncology Group (GOG) or Eastern Cooperative Oncology Group (ECOG)
performance status =< 1 or Karnofsky scale (KPS) =< 70%

- Patients who are platinum-sensitive or platinum resistant

- Candidate for potentially radical, maximal effort cytoreductive surgery at the
discretion and expertise of the treating physician

- For patients with newly diagnosed ovarian/tubal/peritoneal cancer who have received
pre-operative neoadjuvant chemotherapy, evidence of response must be documented by at
least one of the following:

- Decline in serum cancer antigen (CA) 125 level

- At least a 30% decrease in the sum of the longest diameter of target lesions on
radiographic imaging

- Improvement of ascites volume

- Neoadjuvant chemotherapy must be held for at least 3 weeks prior to surgery

- Resolution of any effects of prior (except alopecia and peripheral neuropathy) to
the current National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Events (NCI CTCAE) grade =< 1 and to baseline laboratory values as
defined

- Hemoglobin (HGB) >= 9 g/dL

- White blood cell (WBC) >= 3,000/mcL

- Absolute neutrophil count (ANC) >= 1,500/mcL

- Platelets (PLT) >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase
(SGPT) < 2.5 x institutional upper limit of normal (ULN)

- Creatinine < 1.5 x ULN or creatinine clearance > 60 ml/min according to
Cockcroft-Gault formula

- Neuropathy (sensory and motor) NCI CTCAE grade =< 2

- Prothrombin time (PT) such that international normalized ratio (INR) is < 1.5 (or an
in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic
warfarin or low molecular weight heparin) and a partial thromboplastin time (PTT) <
1.2 times control

- Serum albumin >= 2.5

- No active infection requiring antibiotics

- Preoperative or intraoperative (frozen section) diagnosis of ovarian, peritoneal,
fallopian tubal or uterine cancer

- Surgery achieves either no gross residual disease (R0) or optimal cytoreductive status
defined as no single lesion measuring more than 5.0 mm in its greatest diameter

- Stable from a cardiopulmonary standpoint to continue with prolonged surgery and
anesthesia

Exclusion Criteria:

- Patients with active extra-abdominal disease including active malignant pleural
effusion; patients who have been successfully treated with neoadjuvant chemotherapy
and no longer have (malignant) pleural effusions may be included

- Patients whose disease has progressed following at least 3 cycles of neoadjuvant
chemotherapy as defined by at least one of the following:

- Doubling of serum CA-125 level

- At least a 20% increase in the sum of the longest diameter of target lesions,
taking as reference the smallest sum longest diameter recorded since the
treatment started or the appearance of one or more new lesions

- Clinical deterioration (worsening ascites, carcinomatous ileus, malignant bowel
obstruction, severe hypoalbuminemia, declining performance status)

- Cardiac or pulmonary conditions that preclude aggressive cytoreductive surgery

- Patients whose circumstances do not permit completion of the study or the required
follow-up

- Pregnant, nursing, or of childbearing potential and refuse hysterectomy or bilateral
salpingo-oophorectomy

- Other active invasive malignancies, with the exception of non-melanoma skin cancer and
breast cancer (if without evidence of disease 2 years after completion of treatment)

- Metastatic non-gynecologic or breast primaries

- Sub-optimal resection as their surgical outcome

- Intraoperative frozen section suggesting hepatobiliary, pancreatic, adrenal, or
urinary tract cancer