Minimally-Invasive Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy in Treating Patients with Low-Volume Peritoneal Carcinomatosis

This phase I trial studies a minimally-invasive cytoreduction and hyperthermic intraperitoneal chemotherapy in treating patients with a small amount (low-volume) of peritoneal carcinomatosis, which is a term used to describe the widespread of cancerous tumors in the peritoneal cavity. Minimally-invasive cytoreduction is a less invasive type of surgery for peritoneal carcinomatosis and may have fewer side effects and improve recovery. Drugs used in chemotherapy, such as mitomycin C, cisplatin, and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Heating a chemotherapy solution and infusing it directly into the abdomen may kill more tumor cells. Giving minimally-invasive cytoreduction with hyperthermic intraperitoneal chemotherapy may work better in treating peritoneal carcinomatosis.

Inclusion Criteria

• Capable of providing informed consent
• Histologically confirmed peritoneal carcinomatosis from appendiceal, colorectal, ovarian, or primary mesothelioma, with no systemic metastases
• Evidence of low-volume peritoneal disease defined by a peritoneal carcinomatosis index (PCI) =< 10 based on cross-sectional imaging and/or diagnostic laparoscopy findings
• Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0-2
• Patients who are medically fit for surgery defined as the following
• No parenchymal hepatic metastases
• No cross sectional imaging findings indicative of multi-segmental (> 1 site) small bowel obstruction, or small bowel loops matted together, or gross disease of the small bowel mesentery characterized by distortion, thickening or loss of mesenteric vascular clarity
• No clinical or radiological evidence of hematogenous or distant nodal (retroperitoneal, pelvic, mediastinal, peri-portal or peri-aortic) metastasis
• Absolute neutrophil count (ANC) > 1500/mm^3
• White blood cell count (WBC) > 4000/mm^3
• Platelet count > 150,000/mm^3
• An international normalized ratio (INR) =< 1.5 (patients who are therapeutically anticoagulated for unrelated medical conditions such as atrial fibrillation and whose antithrombotic treatment can be withheld for operation will be eligible)
• Total serum bilirubin =< 1.5 mg/dl (patients with total bilirubin > 1.5 mg/dL eligible only with Gilbert’s syndrome)
• Alkaline phosphatase < 3 times the upper limit of normal (alkaline phosphatase and aspartate aminotransferase [AST] cannot both exceed the upper limit of normal)
• AST < 3 times upper limit of normal (alkaline phosphatase and AST cannot both exceed the upper limit of normal)
• Serum renal functional parameters, blood urea nitrogen (BUN) and creatinine within normal limits
• Creatinine within normal limits
• Satisfactory cardiopulmonary function (no history of severe congestive heart failure or severe pulmonary disease, as indicated by clinically acceptable risks to undergo major abdominal - cytoreductive surgery)
• No clinical history of acute myocardial infarction within six months of registration
• Patients who are status post revascularization procedures with satisfactory cardiac function are eligible
• No significant history of a medical problem or co-morbidity that would preclude the patient from undergoing a major abdominal operation such as a history of severe congestive heart failure or active ischemic heart disease
• No concurrent second malignancy requiring systemic therapy
• No psychiatric or addictive disorders or other conditions that would preclude the patient from meeting the study requirements

Exclusion Criteria

• Peritoneal carcinomatosis index (PCI) >= 10
• Systemic (extraperitoneal) disease, pregnant, incarcerated
• Pregnant and lactating women; women of reproductive age must be willing to use contraception during study therapy

PRIMARY OBJECTIVES:

I. To measure the rate of postoperative complications occurring within 30 days of surgery.

SECONDARY OBJECTIVES:

I. Measure completeness of cytoreduction.

II. Determine time to return of bowel function.

III. Measure length of hospital, and length of intensive-care unit (ICU) stay.

IV. Record post-operative intravenous (IV) narcotic requirements.

V. Determine recurrence free and disease-specific survival.

OUTLINE:

Patients undergo minimally-invasive cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) comprising mitomycin C (primary appendiceal and colorectal cancers); and cisplatin or doxorubicin hydrochloride (primary peritoneal mesothelioma or ovarian primary tumors).

After completion of study treatment, patients are followed up at 2 and 6 weeks, every 3-6 months for 1 year, every 6 months for 2 years, and then yearly for up to 3 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of California San Diego

Principal Investigator
Kaitlyn Kelly

• Primary ID 131071
• Secondary IDs NCI-2014-02176
• Clinicaltrials.gov ID NCT02463877