Heated Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Peritoneal Cancer

Primary Objectives:

To determine the maximum tolerated dose (MTD) of carboplatin given as HIPEC for primary treatment of women with advanced ovarian, peritoneal, and fallopian tube cancers.

Secondary Objectives:

• To determine the dose limiting toxicities of HIPEC carboplatin.
• To describe the pharmacokinetic profile of HIPEC carboplatin.
• To quantify changes in tissue temperature during HIPEC and compare to conventional temperature measures (esophageal and bladder).
• To describe the extent of thermal damage and DNA platinum adduct formation in tissues resulting from HIPEC carboplatin.

OUTLINE: This is a dose escalation study.

Patients receive hyperthermic carboplatin intraperitoneally over 60 minutes during the planned surgical cytoreductive procedure.

Inclusion criteria

• Patients must have histologically or cytologically confirmed, known or highly suspected advanced (International Federation of Gynecology and Obstetrics [FIGO] stage II-IV) ovarian, primary peritoneal, or fallopian tube cancer, scheduled for primary or interval cytoreductive surgery
• If the patient has received pre-operative neoadjuvant chemotherapy, evidence of response must be documented by at least one of the following: decline in serum carcinoma antigen (CA)125 level, at least a 30% decrease in the sum of the longest diameter of target lesions on radiographic imaging, or resolution of ascites or pleural effusion(s)
• Women of all races and ethnic groups are eligible for this trial
• Gynecologic Oncology Group (GOG) performance status =< 2
• Leukocytes >= 3,000/microliter (mcL)
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT))/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Albumin >= 2.5 mg/dL
• Patients for whom the diagnosis of high-grade serous or undifferentiated carcinoma of ovarian, peritoneal, or fallopian tubal origin is confirmed at surgery
• Surgery achieves either no gross residual disease or optimal cytoreductive status defined as no single lesion measuring more than 1 cm in its greatest diameter (this protocol calls for the intentional delay in resection of up to 3 tumors per patient until the HIPEC procedure is complete; the surgeon will identify these tumors as easily resectable from a technical and safety aspect)
• Patients must be stable from cardiopulmonary and hemodynamic standpoints to continue with prolonged surgery and anesthesia
• Provision of written informed consent

Exclusion criteria

• Patients receiving neo-adjuvant chemotherapy whose disease has progressed following at least 3 cycles, defined by at least one of the following: clinical deterioration (new or worsening of existing ascites, carcinomatous ileus, malignant bowel obstruction, declining performance status), new lesion(s) or increase in maximal diameter of > 20% of the two largest target lesions, rising CA-125 (an increase of at least 10% of baseline value that increases over 3 values obtained every 21 days)
• Cardiac or pulmonary conditions that preclude aggressive cytoreductive surgery
• Patients found to have non-gynecologic, uterine, or breast primary at surgery
• Patients with gynecologic malignancy of low-grade serous or borderline histology
• Patients with sub-optimal resection (any single tumor larger than 1 cm)
• Patients with core body temperature > 37 degrees Celsius (C) at completion of cytoreductive surgery and prior to HIPEC
• Patients who are receiving other investigational therapeutic agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study