Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer
Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer
This phase I trial studies the side effects and how well surgery and heated chemotherapy with
 or without non-heated chemotherapy after surgery works in treating patients with ovarian,
 fallopian tube, uterine, or peritoneal cancer. Giving a dose of heated chemotherapy into the
 abdomen during surgery that is done to remove ovarian, fallopian tube, uterine, or peritoneal
 cancer may help lower the risk of the cancer coming back. Giving unheated chemotherapy drugs
 directly into the abdomen after surgery may kill more tumor cells.
PRIMARY OBJECTIVE:

 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.

 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, or recurrent 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 therapy (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 1 year 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