Outcomes in CRS/HIPEC as Initial Treatment of Ovarian, Fallopian Tube and Primary Peritoneal Cancer

Primary endpoints:

- To assess the feasibility of recruitment

- Compare complication rates between the two study arms: CRS with HIPEC and CRS alone.

Secondary endpoints:

- To determine risk factors for morbidity and mortality

- Assess completion rate of 6 cycles of systemic chemotherapy

- To determine progression free survival at 24 months

- To determine overall survival at 1, 3, and 5 years

- Evaluate health related quality of life

Patients who meet study criteria will be randomized into one of two treatment arms: 1)
cytoreductive surgery (CRS) with carboplatin-based hyperthermic intraperitoneal chemotherapy
(HIPEC) followed by IV combination chemotherapy with carboplatin and paclitaxel or 2)
cytoreductive surgery (CRS) alone followed by adjuvant intraperitoneal (IP) and IV
chemotherapy with combination cisplatin and paclitaxel for newly diagnosed advanced stage
(stage III/IV) ovarian, fallopian tube or primary peritoneal cancer. Both study arms will
receive 6 cycles of adjuvant chemotherapy.

Twenty-four patients will undergo CRS with HIPEC performed by surgical and gynecologic
oncologic surgeons at Mercy Medical Center, followed by systemic IV chemotherapy with
carboplatin (AUC=6) and paclitaxel (175mg/m2) for 6 cycles postoperatively.

Twenty-four patients will undergo CRS only performed by surgical and gynecologic oncologic
surgeons at Mercy Medical Center, followed by IV/IP chemotherapy with Day 1: IV paclitaxel
(135 mg/m2), Day 2: IP cisplatin (75 mg/m2), and Day 8: IP paclitaxel (60 mg/m2) for 6 cycles
postoperatively.

Inclusion Criteria:

- Clinical presentation of ovarian, fallopian tube or primary peritoneal cancer

- Stage III/IV disease

- No prior treatment or significant surgery for the management of ovarian, fallopian
tube, or primary peritoneal carcinoma; History of laparoscopic procedures to obtain
diagnostic biopsies will be permitted in the study

- Histological confirmation

- Eastern Cooperative Oncology Group performance status 0-2 or Karnofsky performance
status ≥ 70%

- ≤1 cm residual disease at the completion of the cytoreductive surgery (GOG criteria
for optimally cytoreduction)

- Bone marrow function:

1. Absolute neutrophil count (ANC) ≥1,000/mm3

2. Platelets ≥100,000/mm3

3. Hemoglobin ≥ 8.5 g/dL

- Renal function:

1) Creatinine ≤1.5 times the upper limit of normal or a calculated creatinine
clearance ≥60ml/min

- Hepatic function:

1. Bilirubin ≤1.5 times upper limit of normal

2. Alanine aminotransferase (ALT) ≤3 times upper limit of normal

3. Aspartate aminotransferase (AST) ≤3 times upper limit of normal

- Blood coagulation parameters:

1. Prothrombin time (PT) with International Normalized Ratio of ≤1.5 and a partial
prothrombin time (PTT) ≤1.5 times upper limit of normal

2. For patients on full dose warfarin, in range International Normalized Ratio
(usually between 2 and 3) and

3. Partial prothrombin time (PTT) <1.2 times upper limit of normal

4. Candidate for administration of postoperative standard platinum-based combination
systemic chemotherapy (adequate bone marrow, renal, hepatic function, and blood
coagulation parameters)

Exclusion Criteria:

- Any prior treatment modality for the diagnosis of ovarian, fallopian tube, or primary
peritoneal cancerPrior surgical attempt of cytoreductive surgery

- Stage I/II disease

- Presence of other invasive malignancies or evidence of other cancer within the past 3
years

- Known active acute hepatitis and confirmed diagnosis of HIV

- Active systemic infection that requires use of parenteral antibiotics

- History of acute coronary syndromes (ACS), within the last 6 months, according to AHA
definitions

- New York Heart Association (NYHA) Class II or higher congestive heart failure
according to American Heart Association (AHA) definitions

- Canadian Cardiovascular Society (CCS) Class II or higher angina grade according to AHA
definitions

- Uncontrolled hypertension defined as > 140/90 and not cleared for surgery at time of
consent by cardiologist

- History of cerebral artery disease and prior stroke according to AHA definitions in
the last 6 months

- Renal insufficiency with serum creatinine level ≥1.5 times the upper limit of normal
or calculated creatinine clearance <60 ml/min

- Patients with concurrent severe medical problems unrelated to malignancy that will
preclude compliance with the study or places at an unacceptable risk for participation
in the study determinate by study investigators

- Pregnant women are excluded from this study because carboplatin is category D agent
with the potential of teratogenic effects. Due to potential risk for adverse events in
nursing infants secondary to treatment of the mother with carboplatin, breastfeeding
should be discontinued

- Life expectancy of < 12 weeks